1887

Abstract

The human immunodeficiency virus type 1 (HIV-1) epidemic in China is increasing rapidly at an irrepressible rate. It is caused by HIV-1 subtype B′ in central China. After the full-length genome sequencing of the Henan isolate was performed, the definition of optimal cytotoxic T-lymphocyte (CTL) epitopes across the Henan isolate genome has become crucial for vaccine design. In this study, by using ELISPOT assays with synthetic peptides corresponding to the sequence of the Henan isolate, the identification and analysis of Gag-specific CTL responses among 28 treated and 26 untreated infected paid blood donors (PBDs) from the Henan and Hubei provinces of China are presented. These studies focused on CTL responses restricted by the human leukocyte antigen (HLA)-A2 and -A11 molecules, two of the most prominent HLA-A alleles in the Chinese population. The results suggested that, in the subgroup analysis, the magnitude of response in the infected treated subgroup [median, 93 spot-forming cells (SFCs) per 10 peripheral blood mononuclear cells (PBMCs)] was significantly lower than that in the chronically infected untreated subgroup (median, 221 SFCs per 10 PBMCs), and HLA-A2-restricted treated PBDs had a response of a much higher frequency and magnitude than that of HLA-A11-restricted treated PBDs. Moreover, some novel peptides restricted by the HLA-A2 and -A11 molecules were identified.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81335-0
2006-01-01
2019-11-21
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/1/151.html?itemId=/content/journal/jgv/10.1099/vir.0.81335-0&mimeType=html&fmt=ahah

References

  1. Addo, M. M., Yu, X. G., Rathod, A. & 17 other authors ( 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.[CrossRef]
    [Google Scholar]
  2. Altfeld, M. & Rosenberg, E. S. ( 2000; ). The role of CD4+ T helper cells in the cytotoxic T lymphocyte response to HIV-1. Curr Opin Immunol 12, 375–380.[CrossRef]
    [Google Scholar]
  3. Altman, J. D., Moss, P. A. H., Goulder, P. J. R., Barouch, D. H., McHeyzer-Williams, M. G., Bell, J. I., McMichael, A. J. & Davis, M. M. ( 1996; ). Phenotypic analysis of antigen-specific T lymphocytes. Science 274, 94–96.[CrossRef]
    [Google Scholar]
  4. Bansal, A., Sabbaj, S., Edwards, B. H. & 10 other authors ( 2003; ). T cell responses in HIV type 1-infected adolescent minorities share similar epitope specificities with whites despite significant differences in HLA class I alleles. AIDS Res Hum Retroviruses 19, 1017–1026.[CrossRef]
    [Google Scholar]
  5. Brander, C. & Walker, B. D. ( 1999; ). T lymphocyte responses in HIV-1 infection: implications for vaccine development. Curr Opin Immunol 11, 451–459.[CrossRef]
    [Google Scholar]
  6. Brander, C. & Walker, B. D. ( 2003; ). Gradual adaptation of HIV to human host populations: good or bad news? Nat Med 9, 1359–1362.[CrossRef]
    [Google Scholar]
  7. Bunce, M., Fanning, G. C. & Welsh, K. I. ( 1995; ). Comprehensive, serologically equivalent DNA typing for HLA-B by PCR using sequence-specific primers (PCR-SSP). Tissue Antigens 45, 81–90.[CrossRef]
    [Google Scholar]
  8. Chouquet, C., Autran, B., Gomard, E., Bouley, J. M., Calvez, V., Katlama, C., Costagliola, D. & Riviere, Y. ( 2002; ). Correlation between breadth of memory HIV-specific cytotoxic T cell, viral load and disease progression in HIV infection. AIDS 16, 2399–2407.[CrossRef]
    [Google Scholar]
  9. Frahm, N., Korber, B. T., Adams, C. M. & 24 other authors ( 2004; ). Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities. J Virol 78, 2187–2200.[CrossRef]
    [Google Scholar]
  10. Goulder, P. J. R. ( 2000; ). Rapid characterization of HIV clade C-specific cytotoxic T lymphocyte responses in infected African children and adults. Ann N Y Acad Sci 918, 330–345.
    [Google Scholar]
  11. Goulder, P. J. R., Brander, C., Annamalai, K. & 18 other authors ( 2000; ). Differential narrow focusing of immunodominant human immunodeficiency virus Gag-specific cytotoxic T-lymphocyte responses in infected African and Caucasoid adults and children. J Virol 74, 5679–5690.[CrossRef]
    [Google Scholar]
  12. Kalams, S. A. & Walker, B. D. ( 1998; ). The critical need for CD4 help in maintaining effective cytotoxic T lymphocyte responses. J Exp Med 188, 2199–2204.[CrossRef]
    [Google Scholar]
  13. Kaufman, J. & Jing, J. ( 2002; ). China and AIDS – the time to act is now. Science 296, 2339–2340.[CrossRef]
    [Google Scholar]
  14. Letvin, N. L. ( 1998; ). Progress in the development of an HIV-1 vaccine. Science 280, 1875–1880.[CrossRef]
    [Google Scholar]
  15. Lin, L., Gao, X. & Zhu, W. A. ( 1999; ). Study on HLA-A-C-B haplotype in Chinese with DNA typing. Zhonghua Wei Sheng Wu Xue Yu Mian Yi Xue Za Zhi 19, 152 (in Chinese).
    [Google Scholar]
  16. Novitsky, V., Rybak, N., McLane, M. F. & 13 other authors ( 2001; ). Identification of human immunodeficiency virus type 1 subtype C Gag-, Tat-, Rev-, and Nef-specific Elispot-based cytotoxic T-lymphocyte responses for AIDS vaccine design. J Virol 75, 9210–9228.[CrossRef]
    [Google Scholar]
  17. Novitsky, V., Cao, H., Rybak, N. & 9 other authors ( 2002; ). Magnitude and frequency of cytotoxic T-lymphocyte responses: identification of immunodominant regions of human immunodeficiency virus type 1 subtype C. J Virol 76, 10155–10168.[CrossRef]
    [Google Scholar]
  18. Picker, L. J. & Maino, V. C. ( 2000; ). The CD4+ T cell response to HIV-1. Curr Opin Immunol 12, 381–386.[CrossRef]
    [Google Scholar]
  19. Su, B., Liu, L., Wang, F., Gui, X., Zhao, M., Tien, P., Zhang, L. & Chen, Z. ( 2003; ). HIV-1 subtype B′ dictates the AIDS epidemic among paid blood donors in the Henan and Hubei provinces of China. AIDS 17, 2515–2520.[CrossRef]
    [Google Scholar]
  20. Zou, Y. & Gou, S. ( 1999; ). Study of polymorphism HLA-A locus allele using ARMS/ PCR-SSP on Hunan Hans. Zhonghua Wei Sheng Wu Xue Yu Mian Yi Xue Za Zhi 19, 293–297 (in Chinese).
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81335-0
Loading
/content/journal/jgv/10.1099/vir.0.81335-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error