This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Boon, A. C. M.
Right arrow Articles by Rimmelzwaan, G. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Boon, A. C. M.
Right arrow Articles by Rimmelzwaan, G. F.

 Previous Article  |  Next Article 

Journal of Virology, January 2002, p. 582-590, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.582-590.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Magnitude and Specificity of Influenza A Virus-Specific Cytotoxic T-Lymphocyte Responses in Humans Is Related to HLA-A and -B Phenotype

A. C. M. Boon,1 G. de Mutsert,1 Y. M. F. Graus,2 R. A. M. Fouchier,1 K. Sintnicolaas,3 A. D. M. E. Osterhaus,1 and G. F. Rimmelzwaan1*

Institute of Virology, Erasmus University Rotterdam, 3015 GE Rotterdam,1 Numico Research B. V., 6700 CA Wageningen,2 Bloodbank Rotterdam, Laboratory for Histocompatibility and Immunogenetics, 3318 AS Dordrecht, The Netherlands3

Received 2 July 2001/ Accepted 15 October 2001

The repertoire of human cytotoxic T-lymphocytes (CTL) in response to influenza A viruses has been shown to be directed towards multiple epitopes, with a dominant response to the HLA-A2-restricted M158–66 epitope. These studies, however, were performed with peripheral blood mononuclear cells (PBMC) of individuals selected randomly with respect to HLA phenotype or selected for the expression of one HLA allele without considering an influence of other HLA molecules. In addition, little information is available on the influence of HLA makeup on the overall CTL response against influenza viruses. Here, the influenza A virus-specific CTL response was investigated in groups of HLA-A and -B identical individuals. Between groups the individuals shared two or three of the four HLA-A and -B alleles. After in vitro stimulation of PBMC with influenza virus, the highest CTL activity was found in HLA-A2+ donors. A similar pattern was observed for the precursor frequency of virus-specific CTL (CTLp) ex vivo, with a higher CTLp frequency in HLA-A2-positive donors than in HLA-A2-negative donors, which were unable to recognize the immunodominant M158–66 epitope. In addition, CTL activity and frequency of CTLp for the individual influenza virus epitopes were determined. The frequency of CTLp specific for the HLA-B8-restricted epitope NP380–388 was threefold lower in HLA-B27-positive donors than in HLA-B27-negative donors. In addition, the frequency of CTLp specific for the HLA-A1-restricted epitope NP44–52 was threefold higher in HLA-A1-, -A2-, -B8-, and -B35-positive donors than in other donors, which was confirmed by measuring the CTL activity in vitro. These findings indicate that the epitope specificity of the CTL response is related to the phenotype of the other HLA molecules. Furthermore, the magnitude of the influenza virus-specific CTL response seems dependent on the HLA-A and -B phenotypes.

* Corresponding author. Mailing address: Erasmus University Rotterdam, Institute of Virology, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. Phone: 010-4088066. Fax: 010-4089485. E-mail: rimmelzwaan{at}viro.fgg.eur.nl.

Journal of Virology, January 2002, p. 582-590, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.582-590.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Boon, A. C. M., deBeauchamp, J., Hollmann, A., Luke, J., Kotb, M., Rowe, S., Finkelstein, D., Neale, G., Lu, L., Williams, R. W., Webby, R. J. (2009). Host Genetic Variation Affects Resistance to Infection with a Highly Pathogenic H5N1 Influenza A Virus in Mice. J. Virol. 83: 10417-10426 [Abstract] [Full Text]  
  • Wahl, A., McCoy, W., Schafer, F., Bardet, W., Buchli, R., Fremont, D. H., Hildebrand, W. H. (2009). T-Cell Tolerance for Variability in an HLA Class I-Presented Influenza A Virus Epitope. J. Virol. 83: 9206-9214 [Abstract] [Full Text]  
  • Wahl, A., Schafer, F., Bardet, W., Buchli, R., Air, G. M., Hildebrand, W. H. (2009). HLA class I molecules consistently present internal influenza epitopes. Proc. Natl. Acad. Sci. USA 106: 540-545 [Abstract] [Full Text]  
  • Meyer, V. S., Kastenmuller, W., Gasteiger, G., Franz-Wachtel, M., Lamkemeyer, T., Rammensee, H.-G., Stevanovic, S., Sigurdardottir, D., Drexler, I. (2008). Long-Term Immunity against Actual Poxviral HLA Ligands as Identified by Differential Stable Isotope Labeling. J. Immunol. 181: 6371-6383 [Abstract] [Full Text]  
  • Kreijtz, J. H. C. M., de Mutsert, G., van Baalen, C. A., Fouchier, R. A. M., Osterhaus, A. D. M. E., Rimmelzwaan, G. F. (2008). Cross-Recognition of Avian H5N1 Influenza Virus by Human Cytotoxic T-Lymphocyte Populations Directed to Human Influenza A Virus. J. Virol. 82: 5161-5166 [Abstract] [Full Text]  
  • Kim, H. M., Lee, Y.-W., Lee, K.-J., Kim, H. S., Cho, S. W., van Rooijen, N., Guan, Y., Seo, S. H. (2008). Alveolar Macrophages Are Indispensable for Controlling Influenza Viruses in Lungs of Pigs. J. Virol. 82: 4265-4274 [Abstract] [Full Text]  
  • Stoffels, R. J., Spencer, H. G. (2008). An Asymmetric Model of Heterozygote Advantage at Major Histocompatibility Complex Genes: Degenerate Pathogen Recognition and Intersection Advantage. Genetics 178: 1473-1489 [Abstract] [Full Text]  
  • Simonsen, L., Viboud, C., Grenfell, B. T., Dushoff, J., Jennings, L., Smit, M., Macken, C., Hata, M., Gog, J., Miller, M. A., Holmes, E. C. (2007). The Genesis and Spread of Reassortment Human Influenza A/H3N2 Viruses Conferring Adamantane Resistance. Mol Biol Evol 24: 1811-1820 [Abstract] [Full Text]  
  • Berkhoff, E. G. M., Geelhoed-Mieras, M. M., Fouchier, R. A. M., Osterhaus, A. D. M. E., Rimmelzwaan, G. F. (2007). Assessment of the extent of variation in influenza A virus cytotoxic T-lymphocyte epitopes by using virus-specific CD8+ T-cell clones. J. Gen. Virol. 88: 530-535 [Abstract] [Full Text]  
  • Boon, A. C. M., de Mutsert, G., Fouchier, R. A. M., Osterhaus, A. D. M. E., Rimmelzwaan, G. F. (2006). The Hypervariable Immunodominant NP418-426 Epitope from the Influenza A Virus Nucleoprotein Is Recognized by Cytotoxic T Lymphocytes with High Functional Avidity.. J. Virol. 80: 6024-6032 [Abstract] [Full Text]  
  • Smith, C. L., Mirza, F., Pasquetto, V., Tscharke, D. C., Palmowski, M. J., Dunbar, P. R., Sette, A., Harris, A. L., Cerundolo, V. (2005). Immunodominance of Poxviral-Specific CTL in a Human Trial of Recombinant-Modified Vaccinia Ankara. J. Immunol. 175: 8431-8437 [Abstract] [Full Text]  
  • Berkhoff, E. G. M., de Wit, E., Geelhoed-Mieras, M. M., Boon, A. C. M., Symons, J., Fouchier, R. A. M., Osterhaus, A. D. M. E., Rimmelzwaan, G. F. (2005). Functional Constraints of Influenza A Virus Epitopes Limit Escape from Cytotoxic T Lymphocytes. J. Virol. 79: 11239-11246 [Abstract] [Full Text]  
  • Rimmelzwaan, G. F., Berkhoff, E. G. M., Nieuwkoop, N. J., Smith, D. J., Fouchier, R. A. M., Osterhaus, A. D. M. E. (2005). Full restoration of viral fitness by multiple compensatory co-mutations in the nucleoprotein of influenza A virus cytotoxic T-lymphocyte escape mutants. J. Gen. Virol. 86: 1801-1805 [Abstract] [Full Text]  
  • Tourdot, S., Nejmeddine, M., Powis, S. J., Gould, K. G. (2005). Different MHC Class I Heavy Chains Compete with Each Other for Folding Independently of {beta}2-Microglobulin and Peptide. J. Immunol. 174: 925-933 [Abstract] [Full Text]  
  • Baskin, C. R., Garcia-Sastre, A., Tumpey, T. M., Bielefeldt-Ohmann, H., Carter, V. S., Nistal-Villan, E., Katze, M. G. (2004). Integration of Clinical Data, Pathology, and cDNA Microarrays in Influenza Virus-Infected Pigtailed Macaques (Macaca nemestrina). J. Virol. 78: 10420-10432 [Abstract] [Full Text]  
  • Berkhoff, E. G. M., Boon, A. C. M., Nieuwkoop, N. J., Fouchier, R. A. M., Sintnicolaas, K., Osterhaus, A. D. M. E., Rimmelzwaan, G. F. (2004). A Mutation in the HLA-B*2705-Restricted NP383-391 Epitope Affects the Human Influenza A Virus-Specific Cytotoxic T-Lymphocyte Response In Vitro. J. Virol. 78: 5216-5222 [Abstract] [Full Text]  
  • Boon, A. C. M., de Mutsert, G., Fouchier, R. A. M., Sintnicolaas, K., Osterhaus, A. D. M. E., Rimmelzwaan, G. F. (2004). Preferential HLA Usage in the Influenza Virus-Specific CTL Response. J. Immunol. 172: 4435-4443 [Abstract] [Full Text]  
  • Boon, A. C. M., de Mutsert, G., van Baarle, D., Smith, D. J., Lapedes, A. S., Fouchier, R. A. M., Sintnicolaas, K., Osterhaus, A. D. M. E., Rimmelzwaan, G. F. (2004). Recognition of Homo- and Heterosubtypic Variants of Influenza A Viruses by Human CD8+ T Lymphocytes. J. Immunol. 172: 2453-2460 [Abstract] [Full Text]  
  • Hu, P. Q., Tuma-Warrino, R. J., Bryan, M. A., Mitchell, K. G., Higgins, D. E., Watkins, S. C., Salter, R. D. (2004). Escherichia coli Expressing Recombinant Antigen and Listeriolysin O Stimulate Class I-Restricted CD8+ T Cells following Uptake by Human APC. J. Immunol. 172: 1595-1601 [Abstract] [Full Text]  
  • Leen, A. M., Sili, U., Savoldo, B., Jewell, A. M., Piedra, P. A., Brenner, M. K., Rooney, C. M. (2004). Fiber-modified adenoviruses generate subgroup cross-reactive, adenovirus-specific cytotoxic T lymphocytes for therapeutic applications. Blood 103: 1011-1019 [Abstract] [Full Text]  
  • Gog, J. R., Rimmelzwaan, G. F., Osterhaus, A. D. M. E., Grenfell, B. T. (2003). Population dynamics of rapid fixation in cytotoxic T lymphocyte escape mutants of influenza A. Proc. Natl. Acad. Sci. USA 100: 11143-11147 [Abstract] [Full Text]  
  • Terajima, M., Cruz, J., Raines, G., Kilpatrick, E. D., Kennedy, J. S., Rothman, A. L., Ennis, F. A. (2003). Quantitation of CD8+ T Cell Responses to Newly Identified HLA-A*0201-restricted T Cell Epitopes Conserved Among Vaccinia and Variola (Smallpox) Viruses. JEM 197: 927-932 [Abstract] [Full Text]  
  • Tourdot, S., Gould, K. G. (2002). Competition Between MHC Class I Alleles for Cell Surface Expression Alters CTL Responses to Influenza A Virus. J. Immunol. 169: 5615-5621 [Abstract] [Full Text]  
  • Boon, A. C. M., de Mutsert, G., Graus, Y. M. F., Fouchier, R. A. M., Sintnicolaas, K., Osterhaus, A. D. M. E., Rimmelzwaan, G. F. (2002). Sequence Variation in a Newly Identified HLA-B35-Restricted Epitope in the Influenza A Virus Nucleoprotein Associated with Escape from Cytotoxic T Lymphocytes. J. Virol. 76: 2567-2572 [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»