Previous Article | Next Article 
Journal of Virology, October 1999, p. 8179-8184, Vol. 73, No. 10
Institut für Medizinische Immunologie,
Received 26 April 1999/Accepted 28 June 1999
Cell-mediated immunity plays an essential role in the control of
infection with the human cytomegalovirus (HCMV). However, only a few
CD8+-T-cell epitopes are known, with the majority being
contained in the pp65 phosphoprotein, which is believed to dominate the CD8+-T-cell response to HCMV. Here, we have readdressed the
issue of CD8+ T cells specific for the 72-kDa major
immediate-early protein (IE-1), which is nonstructural but is found
very early and throughout the replicative cycle. Using a novel
flow-cytometric assay, we were able to identify CD8+-T-cell
epitopes (by IE-1 peptide-specific induction of cytokine synthesis) and
simultaneously measure the frequency of cells directed against them.
For this purpose, 81 pentadecamer peptides covering the complete
491-amino-acid sequence of IE-1 were tested on peripheral blood
mononuclear cells of anti-HCMV immunoglobulin G-seropositive donors. At
least 10 new epitopes were identified, and the fine specificity and
presenting HLA molecule of the first of them was determined. The
frequencies of CD8+ T cells directed against IE-1 were
similar to those directed against pp65 in donors tested with known
pp65-derived peptides. Importantly, additional testing of a
corresponding set of peptides covering the complete sequence of pp65 on
10 of these donors identified individuals whose CD8+ T
cells recognized IE-1 but not pp65 and vice versa, clearly illustrating
that either protein may be a major target. In summary, our results
suggest that IE-1 is far more important as a CD8+-T-cell
target than current opinion suggests.
Primary infection with or
reactivation of the human cytomegalovirus (HCMV) is a major
complication after bone marrow transplantation and solid-organ
transplantation, and in persons infected with human immunodeficiency
virus (11, 19-21, 24). Cell-mediated immunity plays an
essential role in the control of persistent infection, induction of
latency, and recovery from acute disease (11, 14, 15, 19-21,
24). Adoptive transfer of HCMV-specific CD8+-T-cell
clones in bone marrow transplant recipients has successfully prevented
viremia and disease (11, 20, 21, 24), illustrating the
importance of a sufficient CD8+-T-cell response in
particular. Boosting the CD8+-T-cell response with
HCMV-derived peptides could potentially be a useful alternative to
adoptive T-cell transfer in these patients. In this regard, a
previously defined HLA-2.1-presented cytotoxic T-lymphocyte (CTL)
epitope from the HCMV pp65 protein is being evaluated as a candidate
for vaccination therapy (5).
Unfortunately, to date, our knowledge of HCMV CD8+-T-cell
epitopes is limited to only a few, most of which originate from the pp65 lower matrix phosphoprotein (UL83) (25) and some of
which originate from the 72-kDa major immediate-early protein (IE-1) (1, 9). The presenting HLA molecules, as far as they are known, are HLA-A2, HLA-B7, HLA-B8, HLA-B18, and HLA-B35 (1, 9,
25), so that only approximately 50 to 60% of a Caucasian population could theoretically benefit from vaccinations or immune therapy based on these known epitopes. Despite the existence of several
CTL epitopes in IE-1 (1, 9) and the observation of
IE-1-directed CTL activity in early studies on the anti-HCMV T-cell
response (2), the pp65 phosphoprotein is presently believed to largely dominate the anti-HCMV CTL response (13, 25).
This is partly because structural proteins, such as pp65, which is presented by infected cells prior to virus protein synthesis, are
thought to be more effective targets per se than are nonstructural proteins (such as IE-1) (13). That major histocompatibility complex class I-presented peptides are typically 9 amino acids long
(16-18) was first revealed in 1991 (8) and later
reflected in the use of at least nine overlaps in the design of
peptides used for epitope mapping. The only major study attempting to
map CTL epitopes in IE-1 was in fact published in 1991 and used only six overlaps between adjacent peptides (1). Because pp65 had only recently been studied with regard to CTL epitopes by using a
modern peptide design (25), we chose IE-1 as the first HCMV protein to readdress the issue of CD8+-T-cell epitopes by
using a novel and very efficient flow cytometry-based method
(12). This new method examines rapid peptide-specific induction of effector cytokine synthesis at the single-cell level (12). For this purpose, 81 15-amino-acid peptides (nine
overlaps between adjacent peptides) derived from the 491-amino-acid
protein sequence of IE-1 (SwissProt accession no. P13202) were tested on peripheral blood mononuclear cells (PBMC) from 20 HCMV-seropositive healthy blood donors. At least 10 15-amino-acid peptides that induced
gamma interferon (IFN- Citrated blood was obtained from HLA-typed HCMV-seropositive
(immunoglobulin G IgG) blood donors. Following standard Ficoll-Paque (Pharmacia, Uppsala, Sweden) density centrifugation, cells were washed
with sterile phosphate-buffered saline (PBS; Gibco-BRL), resuspended in
RPMI 1640 (Biochrom, Berlin, Germany) containing 0.1% (wt/vol) bovine
serum albumin (Biochrom) and 50 mM glutamine (Biochrom), and adjusted
to 107 cells/ml. Then 200 µl each of cell suspensions and
peptide solutions (10 µg/ml in RPMI 1640 containing 0.1% bovine
serum albumin) were placed in Cellstar polystyrene tubes (Greiner,
Frickenhausen, Germany) and placed in an incubator (5° slant) at
37°C under a humidified 5% CO2 atmosphere. After 1 h, 1,600 µl of RPMI 1640 containing 12.5% (vol/vol) fetal calf serum
(Biochrom), 50 mM glutamine, and 12.5 µg of brefeldin A (Sigma,
Munich, Germany) per ml was added. After an additional 5 h, the
cells were washed with cold PBS, resuspended in PBS-1 mM EDTA (Merck,
Darmstadt, Germany), incubated for 10 min at 37°C, and washed again
with cold PBS. After surface staining with monoclonal antibodies (for 30 min at 4°C in the dark), the cells were fixed for 5 min at 37°C
in PBS containing 4% (wt/vol) paraformaldehyde (Merck) and washed in
PBS prior to permeabilization (permeabilizing solution; Becton
Dickinson, Heidelberg, Germany) as specified by the manufacturer. Following intracellular staining, the cells were washed in PBS and
analyzed on a FACScalibur flow cytometer (Becton Dickinson) by using
the CellQuestTM software package. Unstimulated samples were analyzed to
verify the effect of stimulation. Data files were analyzed with
CellQuest or Paint-a-Gate software (Becton Dickinson).
On day 1, candidate peptides were selected according to the results
obtained with pooled peptides. These candidate peptides were tested
individually on day 2. For that purpose, PBMC from day 1 were kept in a
standard incubator. Stimulation was performed with individual peptides
by the same method as on day 1, i.e., with the same concentration of
individual peptides as within the peptide pool. Parallel stimulation
with (noncandidate) control peptides and unstimulated samples was
always performed to rule out unspecific stimulation.
Antibodies and peptides.
Fluorescein isothiocyanate
(FITC)-conjugated anti-IFN- Measurement of peptide-specific induction of IFN- Among the IE-1-derived peptides, IE-1307-321
(EFCRVLCCYVLEETS), IE-1193-207 (ARAKKDELRRKMMYM), and
IE-1199-213 (ELRRKMMYMCYRNIE) were the most frequently
identified. All donors reactive to IE-1307-321 were
HLA-B7, HLA-Bw6, and HLA-Cw7 positive (D1, D2, D3, and D4); however,
donors who were HLA-Cw7 or HLA-Bw6 but not HLA-B7 positive did not
react to this peptide (for example D5, D6, D9, D10, and D11),
identifying HLA-B7 as the presenting allomorph.
To define the epitope contained in IE-1307-321 more
precisely, all seven consecutive 9-amino-acid peptides derived from its
sequence were synthesized (i.e., IE-1307-315,
IE-1308-316, IE-1309-317, through
IE-1313-321) and tested in two donors. Several of these
nonamer peptides were able to stimulate IFN-
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Target Structures of the CD8+-T-Cell
Response to Human Cytomegalovirus: the 72-Kilodalton Major
Immediate-Early Protein Revisited
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
) synthesis in subsets of donors were
identified. For the first one of these, we have now determined the
minimal epitope and the presenting HLA molecule. Interestingly, the
measured CD8+-T-cell frequencies were of the same order of
magnitude as those elicited by known pp65-derived peptides in HLA-A2-
and HLA-B7-positive donors (12). More importantly even,
additional testing with a corresponding set of 15-amino-acid peptides
covering the complete sequence of pp65 in some of the donors identified
several subjects with a strong CD8+-T-cell response against
IE-1 but not pp65. Conversely, we identified several donors who had no
CD8+-T-cell response to IE-1 but did show a response to
pp65-derived peptides. These results may have important implications
with regard to the putative role of IE-1 as a factor in HCMV-associated
immune system pathology. In summary, our results suggest that in some individuals IE-1 may be of the same importance as pp65, and in a subset
who do not have pp65-specific CD8+ T cells, IE-1 may even
dominate the CD8+ immune response (possibly together with
yet unidentified epitopes from other proteins).
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
, phycoerythrin (PE)-conjugated
anti-CD69, Peridinin-chlorophyl-protein (PerCP)-conjugated anti-CD8,
allophyocyanin (APC)-conjugated anti-CD3, and the corresponding
isotype- and fluorescent conjugate-matched control reagents were
purchased from Becton Dickinson. Peptides (synthesized by the standard
Fmoc method) were purchased from NMI (Reutlingen, Germany) or produced
at our own facility. Peptides were stored freeze-dried or in dimethyl
sulfoxide (DMSO) at 4 mg/ml. Peptide pools were generated from peptides
dissolved in DMSO. DMSO concentrations in all assay mixtures were kept
below 0.1% (vol/vol).
RESULTS AND DISCUSSION
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
in
CD8+ T cells is a rapid and efficient way to identify
CD8+-T-cell epitopes (12). By testing 81 overlapping peptides, the complete amino acid sequence of the IE-1
protein was covered. Peptide pools were set up in such a way that every
peptide was contained in exactly two pools. Thus, it was possible to
identify candidate peptides by testing not more than 18 peptide pools
on day 1 (Fig. 1). The following day,
selected candidate peptides were tested individually. For this purpose,
PBMC from the same donors had been kept in complete medium in a
standard incubator overnight. Interestingly, stimulation with
previously identified pp65-derived peptides (12) on days 1 and 2 revealed that this preincubation slightly increased the frequency
of responding CD8+ T cells without increasing nonspecific
stimulation as tested with an irrelevant peptide (Fig. 1, top right).
We believe that this effect was due to preactivation of
antigen-presenting cells and/or a reduction of inhibitory monocytic
activity. The shading in Fig. 1 illustrates how candidate peptides were
chosen. The combination of the two positive pools, 7 and 15, clearly
identifies the candidate peptide 52 (i.e., IE-1307-321,
the only one contained in both pools). Figure
2 corresponds to Fig. 1 and shows the
CD8+-T-cell IFN- responses obtained with six different
pools, the two positive pools and the four "neighboring" negative
pools, 6, 8, 14, and 16. Table 1
summarizes the results from 15 experiments with samples from healthy
HCMV IgG-seropositive donors, which led to the identification of
several CD8+-T-cell-inducing IE-1-derived peptides. Table 1
also shows the results obtained by testing a corresponding set of
15-amino-acid peptides covering the complete sequence of the pp65
protein (SwissProt accession no. P06725) in 10 of these donors.
View larger version (70K):
[in a new window]
FIG. 1.
Design of peptide pools. The numbers of the pools (left
column and top row) are shown in bold. Individual peptides
(n = 81) in these 18 pools correspond to the numbers in
the respective columns and rows, with peptide 1 = IE-11-15, peptide 2 = IE-17-21, etc.,
according to the complete sequence of the 72-kDa major IE protein.
View larger version (39K):
[in a new window]
FIG. 2.
Identification of a CD8+-T-cell inducing
peptide from peptide pools. Stimulation of PBMC from an HCMV
IgG-seropositive donor with overlapping 15-amino-acid peptides
originating from the IE-1 protein. The figure shows results obtained
with six different peptide pools on day 1, two of which (pool 7 and
pool 15) gave positive results, and stimulation with the candidate
peptide IE-1307-321 (EFCRVLCCYVLEETS), the only peptide
contained in both positive pools, on day 2. IFN- -positive events are
highlighted. Results for 50,000 CD3 T cells are displayed in each
diagram. PBMC were stained with anti-IFN--FITC, anti-CD69-PE,
anti-CD8-PerCP, and anti-CD3-APC. Axes show log fluorescence
intensity.
TABLE 1.
Listing of identified CD8+ T cell epitopes in
IE-1 and pp65a
induction. In both
donors, IE-1309-317 induced the highest frequency of
CD8+ T cells (0.84 and 0.64%),
IE-1310-318 gave a somewhat smaller response (0.50 and
0.42%), and two additional consecutive peptides, IE-1309-317 and IE-1310-318, gave
increasingly weak responses (Fig. 3).
These different frequencies of responding CD8+ T cells
obtained in response to stimulation with largely overlapping peptides
suggested that T cells of overlapping or different specificities were
addressed or that, owing to the relatively high concentrations of
peptides we used (on the order of 109 mol/liter), the
incomplete epitope also stimulated T-cell cytokine induction in much
the same way as incomplete epitopes can induce target cell lysis in CTL
assays if their concentrations are high enough (7). This
will have to be examined in additional experiments.
View larger version (63K):
[in a new window]
FIG. 3.
Fine mapping of a 15-amino-acid peptide. According to
the amino acid sequence of the HLA-B7-presented peptide
IE-1307-321 (EFCRVLCCYVLEETS), seven additional nonamer
peptides were synthesized and tested on PBMC of an HLA-B7-positive
donor whose CD8+ T cells were reactive to the original
peptide (top). Several of these nonamer peptides led to IFN-
induction in CD8+ T cells, with IE-1309-317
giving the strongest response (middle and bottom). IFN--positive
events are highlighted. The activation marker CD69 is used to increase
the specificity of the analysis. Results for 50,000 CD8+ T
cells are displayed. PBMC were stained with anti-IFN--FITC,
anti-CD69-PE, anti-CD8-PerCP, and anti-CD3-APC. Axes show log
fluorescence intensity.
Finally, to show that previous infection with CMV was necessary for cytokine induction by IE-1307-321, we tested this peptide on PBMC from three HCMV-seronegative, HLA-B7-positive donors under identical conditions but observed no response (Table 1, bottom). Phorbol myristate acetate/ionomycin stimulation performed in parallel showed that the CD8+ T cells from all individuals were able to produce cytokines upon stimulation. We assumed, therefore, that reactivity to this peptide in our HLA-B7-positive donors was indeed dependent on immunization with HCMV and not likely to result from cross-reactivity with peptides of different origin.
Unlike IE-1307-321, the other identified epitopes did not allow for easy determination of their presenting HLA molecule. Notably, the peptides IE-1193-207 and IE-1199-213 (Table 1) share 9 amino acids, suggesting that in donors who were reactive to both peptides (D5 and D11 [Table 1]) this overlap may define the epitope. Interestingly, computerized binding motif analysis carried out by SYFPEITHI (16), a computer program based on listings of MHC ligands and binding motifs (17, 18) predicted HLA-B8 as the most likely presenting allomorph for this candidate epitope. An even higher score, however, was obtained for HLA-A1 and the decapeptide, IE-1198-207 (DELRRKMMYM [contained only in IE-1193-207]). Nevertheless, at this stage the data is inconclusive, because although HLA-A1 and HLA-B8 are found in all donors reactive to one or both of these peptides (D4, D5, D10, and D11), other donors with just HLA-A1 (D8 and D12), just HLA-B8 (D15), or both HLA-A1 and HLA-B8 (D6) did not respond to either. Fine mapping of the epitope(s) with smaller peptides, however, is likely to give additional clues.
It is important to note that despite the identification of many new
epitopes and high frequencies of CD8+ T cells directed
against them in some donors, samples from other individuals tested with
the complete set of IE-1 peptides showed no response to any of them.
Testing some of our donors with a corresponding set of overlapping
peptides covering the complete 561-amino-acid sequence of pp65
identified several individuals who, despite a strong response to one or
several IE-1-derived peptides, did not respond to any of the
pp65-derived peptides and vice versa. By testing the pp65-derived
peptides, several new epitopes were identified, and some of these are
also shown in Table 1 (the presenting HLA allomorphs are currently
being determined). In some donors, the responses to certain peptides were clearly positive (a distinct population of IFN--positive events
not observed in the control) yet extremely small. For example, in D15,
the frequency of CD8+ T cells responsive to
pp65489-503 and pp65493-507 (both containing
the known epitope pp65495-503) was only 0.02%, while
0.78% responded to the newly identified epitope
pp65205-219. This probably illustrates that when several
different epitopes can be presented, individual peptides may become
dominant epitopes. The same phenomenon may also be observed in other
donors, where single peptides give much stronger responses than others
(Table 1).
In donors reactive to both pp65 and IE-1, the frequencies of responsive CD8+ T cells may be compared; however, it should be noted that the responses obtained with overlapping peptides cannot simply be added, since complete or partial epitopes may be contained in the overlap. More important than the difference in the frequencies of CD8+ T cells responding to one or the other protein in donors responsive to both seems to be the fact that some donors responded to only one of the two proteins. So far we have tested 12 donors with both complete sets of peptides. In total, 7 donors (58%) had IE-1-specific CD8+ T cells, 9 donors (75%) had pp65-specific T cells, and 4 donors (33%) had CD8+ T cells responsive to both proteins. Three donors (25%) responded only to IE-1, and 5 (42%) responded only to pp65. The finding that IE-1-specific CD8+ T cells exist in some but not all individuals may be very important with regard to IE-1-associated immune system pathology (3, 4). IE-1 is known to induce adhesion molecule upregulation in infected cells, which may lead to nonspecific activation of other cells (3, 4). This process is not disrupted by therapy with ganciclovir or foscarnet (4). The role of IE-1-recognizing CD8+ T cells in such a situation will be an interesting subject to study.
Notably, all donors nonresponsive to the pp65 peptides were HLA-A2 or HLA-B7 negative. Conversely, most individuals not responding to IE-1 were HLA-A2 positive and HLA-B7 negative. The data, though preliminary, suggests that preferences for IE-1 over pp65 and vice versa are directly related to the HLA type, and additional studies are in progress to corroborate these results. Dominant peptides may be derived from pp65 or IE-1, and clearly there is no obvious hierarchy of presenting allomorphs at this stage.
Interestingly, Gilbert et al. reported in 1996 that IE-1-specific CTL
were able to lyse IE-1-transfected but not HCMV-infected autologous
fibroblasts (10), and they found that pp65 apparently abrogated IE-1 peptide presentation by restricting its access to the
antigen-processing machinery or diverting it to a different degradation
pathway. This in contrast to earlier data obtained by Borysiewicz et
al., who found that in two subjects, 18 to 58% of the CTL clones able
to lyse HCMV-infected autologous fibroblasts were IE-1 specific
(2). In their study, only a small number of IE-1-specific
CTL clones were unable to lyse HCMV-infected targets. The phenomenon
described by Gilbert et al. may thus apply to only some IE-1-specific
clones. This could be explained if some but not all IE-1 epitopes
escaped presentation under the influence of pp65. Nevertheless, the
high frequencies of IE-1-specific CD8+ T cells in our
donors clearly argue that sufficient presentation of IE-1-derived
peptides takes place for these cells to be generated. It is important
to note in this regard that in HCMV reactivation, IE proteins are
expressed prior to the early protein pp65 (whose expression is
regulated by IE-1- and IE-2-dependent promoters) (22).
Recent studies indicate that HCMV reactivation is a frequent event even
in healthy donors (23), seems to be stress related, and is
probably mediated by tumor necrosis factor alpha (TNF-
) (6,
23).
To compile a selection of epitopes which may be useful for immunotherapy in a majority of the population, additional work must be done. Since the protein-coding content of HCMV is enormous, it will hardly be possible to scan all proteins for epitopes. However, the need to identify T-cell targets in HCMV proteins will increase if vaccination trials using, for example, the A2-presented pp65495-503 are successful (5). Our results should encourage the search for T-cell epitopes in other nonstructural HCMV proteins to complete the repertoire of peptides which may be potential candidates for vaccine development.
| |
FOOTNOTES |
|---|
* Corresponding author. Mailing address: Institut für Medizinische Immunologie der Charité, Campus Mitte, COZ, 10098 Berlin, Germany. Phone: 030-28022858. Fax: 030-28025461. E-mail: florian.kern{at}charite.de.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
|
|---|
| 1. |
Alp, N. J.,
T. D. Allport,
J. Van Zanten,
B. Rodgers,
J. G. Sissons, and L. K. Borysiewicz.
1991.
Fine specificity of cellular immune responses in humans to human cytomegalovirus immediate-early 1 protein.
J. Virol.
65:4812-4820 |
| 2. |
Borysiewicz, L. K.,
J. K. Hickling,
S. Graham,
J. Sinclair,
M. P. Cranage,
G. L. Smith, and J. G. Sissons.
1988.
Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses.
J. Exp. Med.
168:919-931 |
| 3. | Burns, L. J., J. C. Pooley, D. J. Walsh, G. M. Vercellotti, M. L. Weber, and A. Kovacs. 1999. Intercellular adhesion molecule-1 expression in endothelial cells is activated by cytomegalovirus immediate early proteins. Transplantation 67:137-144[Medline]. |
| 4. | Craigen, J. L., and J. E. Grundy. 1996. Cytomegalovirus induced up-regulation of LFA-3 (CD58) and ICAM-1 (CD54) is a direct viral effect that is not prevented by ganciclovir or foscarnet treatment. Transplantation 62:1102-1108[Medline]. |
| 5. |
Diamond, D. J.,
J. York,
J. Y. Sun,
C. L. Wright, and S. J. Forman.
1997.
Development of a candidate HLA A*0201 restricted peptide-based vaccine against human cytomegalovirus infection.
Blood
90:1751-1767 |
| 6. | Docke, W. D., S. Prosch, E. Fietze, V. Kimel, H. Zuckermann, C. Klug, U. Syrbe, H. D. Kruger, R. von Baehr, and H. D. Volk. 1994. Cytomegalovirus reactivation and tumour necrosis factor. Lancet 343:268-269[Medline]. |
| 7. | Falk, K., O. Rotzschke, S. Stevanovic, V. Gnau, K. Sparbier, G. Jung, H.-G. Rammensee, and P. Walden. 1994. Analysis of a naturally occurring HLA class I-restricted viral epitope. Immunology 82:337-342[Medline]. |
| 8. | Falk, K., O. Rotzschke, S. Stevanovic, G. Jung, and H. G. Rammensee. 1991. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351:290-296[Medline]. |
| 9. | Gavin, M. A., M. J. Gilbert, S. R. Riddell, P. D. Greenberg, and M. J. Bevan. 1993. Alkali hydrolysis of recombinant proteins allows for the rapid identification of class I MHC-restricted CTL epitopes. J. Immunol. 151:3971-3980[Abstract]. |
| 10. | Gilbert, M. J., S. R. Riddell, B. Plachter, and P. D. Greenberg. 1996. Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product. Nature 383:720-722[Medline]. |
| 11. | Greenberg, P. D., P. Reusser, J. M. Goodrich, and S. R. Riddell. 1991. Development of a treatment regimen for human cytomegalovirus (CMV) infection in bone marrow transplantation recipients by adoptive transfer of donor-derived CMV-specific T cell clones expanded in vitro. Ann. N. Y. Acad. Sci. 636:184-195[Medline]. |
| 12. | Kern, F., I. P. Surel, C. Brock, B. Freistedt, H. Radtke, A. Scheffold, R. Blasczyk, P. Reinke, J. Schneider-Mergener, A. Radbruch, P. Walden, and H. D. Volk. 1998. T-cell epitope mapping by flow cytometry. Nat. Med. 4:975-978[Medline]. |
| 13. | McLaughlin-Taylor, E., H. Pande, S. J. Forman, B. Tanamachi, C. R. Li, J. A. Zaia, P. D. Greenberg, and S. R. Riddell. 1994. Identification of the major late human cytomegalovirus matrix protein pp65 as a target antigen for CD8+ virus-specific cytotoxic T lymphocytes. J. Med. Virol. 43:103-110[Medline]. |
| 14. | Quinnan, G. V., Jr., W. H. Burns, N. Kirmani, A. H. Rook, J. Manischewitz, L. Jackson, G. W. Santos, and R. Saral. 1984. HLA-restricted cytotoxic T lymphocytes are an early immune response and important defense mechanism in cytomegalovirus infections. Rev. Infect. Dis. 6:156-163[Medline]. |
| 15. | Quinnan, G. V., Jr., N. Kirmani, A. H. Rook, J. F. Manischewitz, L. Jackson, G. Moreschi, G. W. Santos, R. Saral, and W. H. Burns. 1982. Cytotoxic T cells in cytomegalovirus infection: HLA-restricted T-lymphocyte and non-T-lymphocyte cytotoxic responses correlate with recovery from cytomegalovirus infection in bone-marrow-transplant recipients. N. Engl. J. Med. 307:7-13[Abstract]. |
| 16. | Rammensee, H. G., J. Bachmann, N. Emmerich, and S. Stevanovic. 15 January 1999, posting date. SYFPEITHI an Internet
database for MHC ligands and peptide motifs. [Online]
http://134.2.96.221/scripts/hlaserver.dll/home.htm. [20 April
1999, last date accessed.]
|
| 17. | Rammensee, H. G., J. Bachmann, and S. Stevanovic. 1997. MHC ligands and peptide motifs. Landes Bioscience, Georgetown, Tex. |
| 18. | Rammensee, H. G., T. Friede, and S. Stevanovic. 1995. MHC ligands and peptide motifs: first listing. Immunogenetics 41:178-228[Medline]. |
| 19. |
Reusser, P.,
S. R. Riddell,
J. D. Meyers, and P. D. Greenberg.
1991.
Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease.
Blood
78:1373-1380 |
| 20. | Riddell, S. R., P. Reusser, and P. D. Greenberg. 1991. Cytotoxic T cells specific for cytomegalovirus: a potential therapy for immunocompromised patients. Rev. Infect. Dis. 11:966-973. |
| 21. | Riddell, S. R., B. A. Walter, M. J. Gilbert, and P. D. Greenberg. 1994. Selective reconstitution of CD8+ cytotoxic T lymphocyte responses in immunodeficient bone marrow transplant recipients by the adoptive transfer of T cell clones. Bone Marrow Transplant. 4:78-84. |
| 22. | Stenberg, R. M. 1993. Immediate-early genes of human cytomegalovirus: organization and function, p. 330-359. In Y. Becker, G. Darai, and E. S. Huang (ed.), Molecular aspects of human cytomegalovirus diseases. Springer-Verlag KG, Berlin, Germany. |
| 23. | Toro, A. I., and J. Ossa. 1996. PCR activity of CMV in healthy CMV-seropositive individuals: does latency need redefinition? Res. Virol. 147:233-238[Medline]. |
| 24. |
Walter, E. A.,
P. D. Greenberg,
M. J. Gilbert,
R. J. Finch,
K. S. Watanabe,
E. D. Thomas, and S. R. Riddell.
1995.
Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor.
N. Engl. J. Med.
333:1038-1044 |
| 25. | Wills, M. R., A. J. Carmichael, K. Mynard, X. Jin, M. P. Weekes, B. Plachter, and J. G. Sissons. 1996. The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65: frequency, specificity, and T-cell receptor usage of pp65-specific CTL. J. Virol. 70:7569-7579[Abstract]. |
Journal of Virology, October 1999, p. 8179-8184, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Gras, S., Saulquin, X., Reiser, J.-B., Debeaupuis, E., Echasserieau, K., Kissenpfennig, A., Legoux, F., Chouquet, A., Le Gorrec, M., Machillot, P., Neveu, B., Thielens, N., Malissen, B., Bonneville, M., Housset, D.
(2009). Structural Bases for the Affinity-Driven Selection of a Public TCR against a Dominant Human Cytomegalovirus Epitope. J. Immunol.
183: 430-437
[Abstract] [Full Text] -
Liu, J., Ruckwardt, T. J., Chen, M., Johnson, T. R., Graham, B. S.
(2009). Characterization of Respiratory Syncytial Virus M- and M2-Specific CD4 T Cells in a Murine Model. J. Virol.
83: 4934-4941
[Abstract] [Full Text] -
Jagannathan, P., Osborne, C. M., Royce, C., Manion, M. M., Tilton, J. C., Li, L., Fischer, S., Hallahan, C. W., Metcalf, J. A., McLaughlin, M., Pipeling, M., McDyer, J. F., Manley, T. J., Meier, J. L., Altman, J. D., Hertel, L., Davey, R. T. Jr., Connors, M., Migueles, S. A.
(2009). Comparisons of CD8+ T Cells Specific for Human Immunodeficiency Virus, Hepatitis C Virus, and Cytomegalovirus Reveal Differences in Frequency, Immunodominance, Phenotype, and Interleukin-2 Responsiveness. J. Virol.
83: 2728-2742
[Abstract] [Full Text] -
Noriega, V. M., Tortorella, D.
(2009). Human Cytomegalovirus-Encoded Immune Modulators Partner To Downregulate Major Histocompatibility Complex Class I Molecules. J. Virol.
83: 1359-1367
[Abstract] [Full Text] -
Crough, T., Khanna, R.
(2009). Immunobiology of Human Cytomegalovirus: from Bench to Bedside. Clin. Microbiol. Rev.
22: 76-98
[Abstract] [Full Text] -
Wilhelmi, V., Simon, C. O., Podlech, J., Bohm, V., Daubner, T., Emde, S., Strand, D., Renzaho, A., Lemmermann, N. A. W., Seckert, C. K., Reddehase, M. J., Grzimek, N. K. A.
(2008). Transactivation of Cellular Genes Involved in Nucleotide Metabolism by the Regulatory IE1 Protein of Murine Cytomegalovirus Is Not Critical for Viral Replicative Fitness in Quiescent Cells and Host Tissues. J. Virol.
82: 9900-9916
[Abstract] [Full Text] -
Mersseman, V., Besold, K., Reddehase, M. J., Wolfrum, U., Strand, D., Plachter, B., Reyda, S.
(2008). Exogenous introduction of an immunodominant peptide from the non-structural IE1 protein of human cytomegalovirus into the MHC class I presentation pathway by recombinant dense bodies. J. Gen. Virol.
89: 369-379
[Abstract] [Full Text] -
Vescovini, R., Biasini, C., Fagnoni, F. F., Telera, A. R., Zanlari, L., Pedrazzoni, M., Bucci, L., Monti, D., Medici, M. C., Chezzi, C., Franceschi, C., Sansoni, P.
(2007). Massive Load of Functional Effector CD4+ and CD8+ T Cells against Cytomegalovirus in Very Old Subjects. J. Immunol.
179: 4283-4291
[Abstract] [Full Text] -
Day, E. K., Carmichael, A. J., ten Berge, I. J. M., Waller, E. C. P., Sissons, J. G. P., Wills, M. R.
(2007). Rapid CD8+ T Cell Repertoire Focusing and Selection of High-Affinity Clones into Memory Following Primary Infection with a Persistent Human Virus: Human Cytomegalovirus. J. Immunol.
179: 3203-3213
[Abstract] [Full Text] -
Egli, A., Binggeli, S., Bodaghi, S., Dumoulin, A., Funk, G. A., Khanna, N., Leuenberger, D., Gosert, R., Hirsch, H. H.
(2007). Cytomegalovirus and polyomavirus BK posttransplant. Nephrol Dial Transplant
22: viii72-viii82
[Abstract] [Full Text] -
Inokuma, M., dela Rosa, C., Schmitt, C., Haaland, P., Siebert, J., Petry, D., Tang, M., Suni, M. A., Ghanekar, S. A., Gladding, D., Dunne, J. F., Maino, V. C., Disis, M. L., Maecker, H. T.
(2007). Functional T Cell Responses to Tumor Antigens in Breast Cancer Patients Have a Distinct Phenotype and Cytokine Signature. J. Immunol.
179: 2627-2633
[Abstract] [Full Text] -
Miles, D. J. C., van der Sande, M., Jeffries, D., Kaye, S., Ismaili, J., Ojuola, O., Sanneh, M., Touray, E. S., Waight, P., Rowland-Jones, S., Whittle, H., Marchant, A.
(2007). Cytomegalovirus Infection in Gambian Infants Leads to Profound CD8 T-Cell Differentiation. J. Virol.
81: 5766-5776
[Abstract] [Full Text] -
Besold, K., Frankenberg, N., Pepperl-Klindworth, S., Kuball, J., Theobald, M., Hahn, G., Plachter, B.
(2007). Processing and MHC class I presentation of human cytomegalovirus pp65-derived peptides persist despite gpUS2-11-mediated immune evasion. J. Gen. Virol.
88: 1429-1439
[Abstract] [Full Text] -
Khan, N., Best, D., Bruton, R., Nayak, L., Rickinson, A. B., Moss, P. A. H.
(2007). T Cell Recognition Patterns of Immunodominant Cytomegalovirus Antigens in Primary and Persistent Infection. J. Immunol.
178: 4455-4465
[Abstract] [Full Text] -
Delmas, S., Martin, L., Baron, M., Nelson, J. A., Streblow, D. N., Davignon, J.-L.
(2005). Optimization of CD4+ T Lymphocyte Response to Human Cytomegalovirus Nuclear IE1 Protein through Modifications of Both Size and Cellular Localization. J. Immunol.
175: 6812-6819
[Abstract] [Full Text] -
Trautmann, L., Rimbert, M., Echasserieau, K., Saulquin, X., Neveu, B., Dechanet, J., Cerundolo, V., Bonneville, M.
(2005). Selection of T Cell Clones Expressing High-Affinity Public TCRs within Human Cytomegalovirus-Specific CD8 T Cell Responses. J. Immunol.
175: 6123-6132
[Abstract] [Full Text] -
Straathof, K. C., Leen, A. M., Buza, E. L., Taylor, G., Huls, M. H., Heslop, H. E., Rooney, C. M., Bollard, C. M.
(2005). Characterization of Latent Membrane Protein 2 Specificity in CTL Lines from Patients with EBV-Positive Nasopharyngeal Carcinoma and Lymphoma. J. Immunol.
175: 4137-4147
[Abstract] [Full Text] -
Sylwester, A. W., Mitchell, B. L., Edgar, J. B., Taormina, C., Pelte, C., Ruchti, F., Sleath, P. R., Grabstein, K. H., Hosken, N. A., Kern, F., Nelson, J. A., Picker, L. J.
(2005). Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. JEM
202: 673-685
[Abstract] [Full Text] -
Sacre, K., Carcelain, G., Cassoux, N., Fillet, A.-M., Costagliola, D., Vittecoq, D., Salmon, D., Amoura, Z., Katlama, C., Autran, B.
(2005). Repertoire, diversity, and differentiation of specific CD8 T cells are associated with immune protection against human cytomegalovirus disease. JEM
201: 1999-2010
[Abstract] [Full Text] -
Bunde, T., Kirchner, A., Hoffmeister, B., Habedank, D., Hetzer, R., Cherepnev, G., Proesch, S., Reinke, P., Volk, H.-D., Lehmkuhl, H., Kern, F.
(2005). Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells. JEM
201: 1031-1036
[Abstract] [Full Text] -
Trivedi, D., Williams, R. Y., O'Reilly, R. J., Koehne, G.
(2005). Generation of CMV-specific T lymphocytes using protein-spanning pools of pp65-derived overlapping pentadecapeptides for adoptive immunotherapy. Blood
105: 2793-2801
[Abstract] [Full Text] -
Sadagopal, S., Amara, R. R., Montefiori, D. C., Wyatt, L. S., Staprans, S. I., Kozyr, N. L., McClure, H. M., Moss, B., Robinson, H. L.
(2005). Signature for Long-Term Vaccine-Mediated Control of a Simian and Human Immunodeficiency Virus 89.6P Challenge: Stable Low-Breadth and Low-Frequency T-Cell Response Capable of Coproducing Gamma Interferon and Interleukin-2. J. Virol.
79: 3243-3253
[Abstract] [Full Text] -
Khan, N., Bruton, R., Taylor, G. S., Cobbold, M., Jones, T. R., Rickinson, A. B., Moss, P. A. H.
(2005). Identification of Cytomegalovirus-Specific Cytotoxic T Lymphocytes In Vitro Is Greatly Enhanced by the Use of Recombinant Virus Lacking the US2 to US11 Region or Modified Vaccinia Virus Ankara Expressing Individual Viral Genes. J. Virol.
79: 2869-2879
[Abstract] [Full Text] -
Manley, T. J., Luy, L., Jones, T., Boeckh, M., Mutimer, H., Riddell, S. R.
(2004). Immune evasion proteins of human cytomegalovirus do not prevent a diverse CD8+ cytotoxic T-cell response in natural infection. Blood
104: 1075-1082
[Abstract] [Full Text] -
Ferrari, G., Neal, W., Ottinger, J., Jones, A. M., Edwards, B. H., Goepfert, P., Betts, M. R., Koup, R. A., Buchbinder, S., McElrath, M. J., Tartaglia, J., Weinhold, K. J.
(2004). Absence of Immunodominant Anti-Gag p17 (SL9) Responses among Gag CTL-Positive, HIV-Uninfected Vaccine Recipients Expressing the HLA-A*0201 Allele. J. Immunol.
173: 2126-2133
[Abstract] [Full Text] -
Wang, Z., La Rosa, C., Mekhoubad, S., Lacey, S. F., Villacres, M. C., Markel, S., Longmate, J., Ellenhorn, J. D. I., Siliciano, R. F., Buck, C., Britt, W. J., Diamond, D. J.
(2004). Attenuated poxviruses generate clinically relevant frequencies of CMV-specific T cells. Blood
104: 847-856
[Abstract] [Full Text] -
Pelte, C., Cherepnev, G., Wang, Y., Schoenemann, C., Volk, H.-D., Kern, F.
(2004). Random Screening of Proteins for HLA-A*0201-Binding Nine-Amino Acid Peptides Is Not Sufficient for Identifying CD8 T Cell Epitopes Recognized in the Context of HLA-A*0201. J. Immunol.
172: 6783-6789
[Abstract] [Full Text] -
Li Pira, G., Bottone, L., Ivaldi, F., Pelizzoli, R., Del Galdo, F., Lozzi, L., Bracci, L., Loregian, A., Palu, G., De Palma, R., Einsele, H., Manca, F.
(2004). Identification of new Th peptides from the cytomegalovirus protein pp65 to design a peptide library for generation of CD4 T cell lines for cellular immunoreconstitution. Int Immunol
16: 635-642
[Abstract] [Full Text] -
Gibson, L., Piccinini, G., Lilleri, D., Revello, M. G., Wang, Z., Markel, S., Diamond, D. J., Luzuriaga, K.
(2004). Human Cytomegalovirus Proteins pp65 and Immediate Early Protein 1 Are Common Targets for CD8+ T Cell Responses in Children with Congenital or Postnatal Human Cytomegalovirus Infection. J. Immunol.
172: 2256-2264
[Abstract] [Full Text] -
Brown, K., Gao, W., Alber, S., Trichel, A., Murphey-Corb, M., Watkins, S. C., Gambotto, A., Barratt-Boyes, S. M.
(2003). Adenovirus-Transduced Dendritic Cells Injected into Skin or Lymph Node Prime Potent Simian Immunodeficiency Virus-Specific T Cell Immunity in Monkeys. J. Immunol.
171: 6875-6882
[Abstract] [Full Text] -
Gandhi, M. K., Wills, M. R., Okecha, G., Day, E. K., Hicks, R., Marcus, R. E., Sissons, J. G. P., Carmichael, A. J.
(2003). Late diversification in the clonal composition of human cytomegalovirus-specific CD8+ T cells following allogeneic hemopoietic stem cell transplantation. Blood
102: 3427-3438
[Abstract] [Full Text] -
Karlsson, A. C., Deeks, S. G., Barbour, J. D., Heiken, B. D., Younger, S. R., Hoh, R., Lane, M., Sallberg, M., Ortiz, G. M., Demarest, J. F., Liegler, T., Grant, R. M., Martin, J. N., Nixon, D. F.
(2003). Dual Pressure from Antiretroviral Therapy and Cell-Mediated Immune Response on the Human Immunodeficiency Virus Type 1 Protease Gene. J. Virol.
77: 6743-6752
[Abstract] [Full Text] -
Prod'homme, V., Retiere, C., Valtcheva, R., Bonneville, M., Hallet, M.-M.
(2003). Cross-Reactivity of HLA-B*1801-Restricted T-Lymphocyte Clones with Target Cells Expressing Variants of the Human Cytomegalovirus 72kDa-IE1 Protein. J. Virol.
77: 7139-7142
[Abstract] [Full Text] -
Gallez-Hawkins, G., Villacres, M. C., Li, X., Sanborn, M. C., Lomeli, N. A., Zaia, J. A.
(2003). Use of Transgenic HLA A*0201/Kb and HHD II Mice To Evaluate Frequency of Cytomegalovirus IE1-Derived Peptide Usage in Eliciting Human CD8 Cytokine Response. J. Virol.
77: 4457-4462
[Abstract] [Full Text] -
Gamadia, L. E., Remmerswaal, E. B. M., Weel, J. F., Bemelman, F., van Lier, R. A. W., Ten Berge, I. J. M.
(2003). Primary immune responses to human CMV: a critical role for IFN-gamma -producing CD4+ T cells in protection against CMV disease. Blood
101: 2686-2692
[Abstract] [Full Text] -
Karrer, U., Sierro, S., Wagner, M., Oxenius, A., Hengel, H., Koszinowski, U. H., Phillips, R. E., Klenerman, P.
(2003). Memory Inflation: Continuous Accumulation of Antiviral CD8+ T Cells Over Time. J. Immunol.
170: 2022-2029
[Abstract] [Full Text] -
Prod'homme, V., Retiere, C., Imbert-Marcille, B.-M., Bonneville, M., Hallet, M.-M.
(2003). Modulation of HLA-A*0201-Restricted T Cell Responses by Natural Polymorphism in the IE1315-324 Epitope of Human Cytomegalovirus. J. Immunol.
170: 2030-2036
[Abstract] [Full Text] -
Addo, M. M., Yu, X. G., Rathod, A., Cohen, D., Eldridge, R. L., Strick, D., Johnston, M. N., Corcoran, C., Wurcel, A. G., Fitzpatrick, C. A., Feeney, M. E., Rodriguez, W. R., Basgoz, N., Draenert, R., Stone, D. R., Brander, C., Goulder, P. J. R., Rosenberg, E. S., Altfeld, M., Walker, B. D.
(2003). Comprehensive Epitope Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Responses Directed against the Entire Expressed HIV-1 Genome Demonstrate Broadly Directed Responses, but No Correlation to Viral Load. J. Virol.
77: 2081-2092
[Abstract] [Full Text] -
Lenfant, F., Pizzato, N., Liang, S., Davrinche, C., Le Bouteiller, P., Horuzsko, A.
(2003). Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice. J. Gen. Virol.
84: 307-317
[Abstract] [Full Text] -
Khan, N., Shariff, N., Cobbold, M., Bruton, R., Ainsworth, J. A., Sinclair, A. J., Nayak, L., Moss, P. A. H.
(2002). Cytomegalovirus Seropositivity Drives the CD8 T Cell Repertoire Toward Greater Clonality in Healthy Elderly Individuals. J. Immunol.
169: 1984-1992
[Abstract] [Full Text] -
Le Roy, E., Baron, M., Faigle, W., Clement, D., Lewinsohn, D. M., Streblow, D. N., Nelson, J. A., Amigorena, S., Davignon, J.-L.
(2002). Infection of APC by Human Cytomegalovirus Controlled Through Recognition of Endogenous Nuclear Immediate Early Protein 1 by Specific CD4+ T Lymphocytes. J. Immunol.
169: 1293-1301
[Abstract] [Full Text] -
Wills, M R, Carmichael, A J, Sissons, J G P
(2002). Vaccines against persistent DNA virus infections. Br Med Bull
62: 125-138
[Abstract] [Full Text] -
Amara, R. R., Villinger, F., Staprans, S. I., Altman, J. D., Montefiori, D. C., Kozyr, N. L., Xu, Y., Wyatt, L. S., Earl, P. L., Herndon, J. G., McClure, H. M., Moss, B., Robinson, H. L.
(2002). Different Patterns of Immune Responses but Similar Control of a Simian-Human Immunodeficiency Virus 89.6P Mucosal Challenge by Modified Vaccinia Virus Ankara (MVA) and DNA/MVA Vaccines. J. Virol.
76: 7625-7631
[Abstract] [Full Text] -
Wills, M. R., Okecha, G., Weekes, M. P., Gandhi, M. K., Sissons, P. J. G., Carmichael, A. J.
(2002). Identification of Naive or Antigen-Experienced Human CD8+ T Cells by Expression of Costimulation and Chemokine Receptors: Analysis of the Human Cytomegalovirus-Specific CD8+ T Cell Response. J. Immunol.
168: 5455-5464
[Abstract] [Full Text] -
Amara, R. R., Smith, J. M., Staprans, S. I., Montefiori, D. C., Villinger, F., Altman, J. D., O'Neil, S. P., Kozyr, N. L., Xu, Y., Wyatt, L. S., Earl, P. L., Herndon, J. G., McNicholl, J. M., McClure, H. M., Moss, B., Robinson, H. L.
(2002). Critical Role for Env as well as Gag-Pol in Control of a Simian-Human Immunodeficiency Virus 89.6P Challenge by a DNA Prime/Recombinant Modified Vaccinia Virus Ankara Vaccine. J. Virol.
76: 6138-6146
[Abstract] [Full Text] -
Morello, C. S., Ye, M., Spector, D. H.
(2002). Development of a Vaccine against Murine Cytomegalovirus (MCMV), Consisting of Plasmid DNA and Formalin-Inactivated MCMV, That Provides Long-Term, Complete Protection against Viral Replication. J. Virol.
76: 4822-4835
[Abstract] [Full Text] -
Moutaftsi, M., Mehl, A. M., Borysiewicz, L. K., Tabi, Z.
(2002). Human cytomegalovirus inhibits maturation and impairs function of monocyte-derived dendritic cells. Blood
99: 2913-2921
[Abstract] [Full Text] -
Holtappels, R., Thomas, D., Podlech, J., Reddehase, M. J.
(2002). Two Antigenic Peptides from Genes m123 and m164 of Murine Cytomegalovirus Quantitatively Dominate CD8 T-Cell Memory in the H-2d Haplotype. J. Virol.
76: 151-164
[Abstract] [Full Text] -
Peggs, K., Verfuerth, S., Pizzey, A., Ainsworth, J., Moss, P., Mackinnon, S.
(2002). Characterization of human cytomegalovirus peptide-specific CD8+ T-cell repertoire diversity following in vitro restimulation by antigen-pulsed dendritic cells. Blood
99: 213-223
[Abstract] [Full Text] -
Gallot, G., Vivien, R., Ibisch, C., Lule, J., Davrinche, C., Gaschet, J., Vie, H.
(2001). Purification of Ag-Specific T Lymphocytes After Direct Peripheral Blood Mononuclear Cell Stimulation Followed by CD25 Selection. I. Application to CD4+ or CD8+ Cytomegalovirus Phosphoprotein pp65 Epitope Determination. J. Immunol.
167: 4196-4206
[Abstract] [Full Text] -
Vaz-Santiago, J., Lule, J., Rohrlich, P., Jacquier, C., Gibert, N., Le Roy, E., Betbeder, D., Davignon, J.-L., Davrinche, C.
(2001). Ex Vivo Stimulation and Expansion of both CD4+ and CD8+ T Cells from Peripheral Blood Mononuclear Cells of Human Cytomegalovirus-Seropositive Blood Donors by Using a Soluble Recombinant Chimeric Protein, IE1-pp65. J. Virol.
75: 7840-7847
[Abstract] [Full Text] -
Gratama, J. W., van Esser, J. W. J., Lamers, C. H. J., Tournay, C., Lowenberg, B., Bolhuis, R. L. H., Cornelissen, J. J.
(2001). Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection. Blood
98: 1358-1364
[Abstract] [Full Text] -
Bitmansour, A. D., Waldrop, S. L., Pitcher, C. J., Khatamzas, E., Kern, F., Maino, V. C., Picker, L. J.
(2001). Clonotypic Structure of the Human CD4+ Memory T Cell Response to Cytomegalovirus. J. Immunol.
167: 1151-1163
[Abstract] [Full Text] -
Gamadia, L. E., Rentenaar, R. J., Baars, P. A., Remmerswaal, E. B. M., Surachno, S., Weel, J. F. L., Toebes, M., Schumacher, T. N. M., ten Berge, I. J. M., van Lier, R. A. W.
(2001). Differentiation of cytomegalovirus-specific CD8+ T cells in healthy and immunosuppressed virus carriers. Blood
98: 754-761
[Abstract] [Full Text] -
Casazza, J. P., Betts, M. R., Picker, L. J., Koup, R. A.
(2001). Decay Kinetics of Human Immunodeficiency Virus-Specific CD8+ T Cells in Peripheral Blood after Initiation of Highly Active Antiretroviral Therapy. J. Virol.
75: 6508-6516
[Abstract] [Full Text] -
Novak, E. J., Liu, A. W., Gebe, J. A., Falk, B. A., Nepom, G. T., Koelle, D. M., Kwok, W. W.
(2001). Tetramer-Guided Epitope Mapping: Rapid Identification and Characterization of Immunodominant CD4+ T Cell Epitopes from Complex Antigens. J. Immunol.
166: 6665-6670
[Abstract] [Full Text] -
Tabi, Z., Moutaftsi, M., Borysiewicz, L. K.
(2001). Human Cytomegalovirus pp65- and Immediate Early 1 Antigen-Specific HLA Class I-Restricted Cytotoxic T Cell Responses Induced by Cross-Presentation of Viral Antigens. J. Immunol.
166: 5695-5703
[Abstract] [Full Text] -
Koelle, D. M., Chen, H. B., Gavin, M. A., Wald, A., Kwok, W. W., Corey, L.
(2001). CD8 CTL from Genital Herpes Simplex Lesions: Recognition of Viral Tegument and Immediate Early Proteins and Lysis of Infected Cutaneous Cells. J. Immunol.
166: 4049-4058
[Abstract] [Full Text] -
Peggs, K., Verfuerth, S., Mackinnon, S.
(2001). Induction of cytomegalovirus (CMV)-specific T-cell responses using dendritic cells pulsed with CMV antigen: a novel culture system free of live CMV virions. Blood
97: 994-1000
[Abstract] [Full Text] -
Lewinsohn, D. M., Zhu, L., Madison, V. J., Dillon, D. C., Fling, S. P., Reed, S. G., Grabstein, K. H., Alderson, M. R.
(2001). Classically Restricted Human CD8+ T Lymphocytes Derived from Mycobacterium tuberculosis-Infected Cells: Definition of Antigenic Specificity. J. Immunol.
166: 439-446
[Abstract] [Full Text] -
Holtappels, R., Thomas, D., Reddehase, M. J.
(2000). Identification of a Kd-restricted antigenic peptide encoded by murine cytomegalovirus early gene M84. J. Gen. Virol.
81: 3037-3042
[Abstract] [Full Text] -
Betts, M. R., Casazza, J. P., Patterson, B. A., Waldrop, S., Trigona, W., Fu, T.-M., Kern, F., Picker, L. J., Koup, R. A.
(2000). Putative Immunodominant Human Immunodeficiency Virus-Specific CD8+ T-Cell Responses Cannot Be Predicted by Major Histocompatibility Complex Class I Haplotype. J. Virol.
74: 9144-9151
[Abstract] [Full Text] -
Pepperl, S., Münster, J., Mach, M., Harris, J. R., Plachter, B.
(2000). Dense Bodies of Human Cytomegalovirus Induce both Humoral and Cellular Immune Responses in the Absence of Viral Gene Expression. J. Virol.
74: 6132-6146
[Abstract] [Full Text] -
Retière, C., Prod'homme, V., Imbert-Marcille, B.-M., Bonneville, M., Vié, H., Hallet, M.-M.
(2000). Generation of Cytomegalovirus-Specific Human T-Lymphocyte Clones by Using Autologous B-Lymphoblastoid Cells with Stable Expression of pp65 or IE1 Proteins: a Tool To Study the Fine Specificity of the Antiviral Response. J. Virol.
74: 3948-3952
[Abstract] [Full Text] -
Morello, C. S., Cranmer, L. D., Spector, D. H.
(2000). Suppression of Murine Cytomegalovirus (MCMV) Replication with a DNA Vaccine Encoding MCMV M84 (a Homolog of Human Cytomegalovirus pp65). J. Virol.
74: 3696-3708
[Abstract] [Full Text] -
Zaia, J. A., Sissons, J.G. P., Riddell, S., Diamond, D. J., Wills, M.R., Carmichael, A.J., Weekes, M.P., Gandhi, M., La Rosa, C., Villacres, M., Lacey, S., Markel, S., Sun, J.
(2000). Status of Cytomegalovirus Prevention and Treatment in 2000. ASH Education Book
2000: 339-355
[Abstract] [Full Text]
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»