This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alp, N J Articles by Borysiewicz, L K Search for Related Content PubMed PubMed Citation Articles by Alp, N J Articles by Borysiewicz, L K

 Previous Article  |  Next Article 

J Virol. 1991 September; 65(9): 4812-4820

Fine specificity of cellular immune responses in humans to human cytomegalovirus immediate-early 1 protein.

Department of Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.

ABSTRACT

Cell-mediated immunity is important in maintaining the virus-host equilibrium in persistent human cytomegalovirus (HCMV) infection. The HCMV 72-kDa major immediate early 1 protein (IE1) is a target for CD8+ cytotoxic T cells in humans, as is the equivalent 89-kDa protein in mouse. Less is known about responses against this protein by CD4+ T cells, which may be important as direct effector cells or helper cells for antibody and CD8+ responses. Proliferative-T-cell responses to HCMV IE1 were studied in normal seropositive subjects. Peripheral blood mononuclear cells from 85% of seropositive subjects proliferated in response to HCMV from infected fibroblasts, and of these, 73% responded to recombinant baculovirus IE1. Responding cells were predominantly CD3+ CD4+. IE1 antigen preparations, including baculovirus recombinant protein, transfected rat cell nuclei, and synthetic peptides, induced IE1-specific T-cell lines which cross-reacted between the preparations. The fine specificity of these IE1-specific T-cell lines was studied by using overlapping synthetic peptides encompassing the entire sequence of the IE1 protein. The regions of the IE1 molecule recognized were identified and these varied between individuals, possibly reflecting differences in major histocompatibility complex (MHC) class II haplotype. In one subject, the peptide specificities of proliferative and MHC class I-restricted cytotoxic determinants on IE1 were spatially distinct. Thus, no single immunodominant T-cell determinant within HCMV IE1 was identified, suggesting that multiple peptides or a region of the 72-kDa IE1 protein would be required to induce specific T-cell responses in humans.

This article has been cited by other articles:

• 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. J. Exp. Med. 202: 673-685 [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]  
• 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]  
• 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]  
• 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]  
• 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]  
• 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]  
• Kern, F., Surel, I. P., Faulhaber, N., Frommel, C., Schneider-Mergener, J., Schonemann, C., Reinke, P., Volk, H.-D. (1999). Target Structures of the CD8+-T-Cell Response to Human Cytomegalovirus: the 72-Kilodalton Major Immediate-Early Protein Revisited. J. Virol. 73: 8179-8184 [Abstract] [Full Text]  
• Le Roy, E., Mühlethaler-Mottet, A., Davrinche, C., Mach, B., Davignon, J.-L. (1999). Escape of Human Cytomegalovirus from HLA-DR-Restricted CD4+ T-Cell Response Is Mediated by Repression of Gamma Interferon-Induced Class II Transactivator Expression. J. Virol. 73: 6582-6589 [Abstract] [Full Text]