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Virus-specific CD8(+) T cells are known to play an important role in the control of HIV infection. In this study we investigated whether there may be qualitative differences in the CD8(+) T cell response in HIV-1- and HIV-2-infected individuals that contribute to the relatively efficient control of the latter infection. A molecular comparison of global TCR heterogeneity showed a more oligoclonal pattern of CD8 cells in HIV-1- than HIV-2-infected patients. This was reflected in restricted and conserved TCR usage by CD8(+) T cells recognizing individual HLA-A2- and HLA-B57-restricted viral epitopes in HIV-1, with limited plasticity in their response to amino acid substitutions within these epitopes. The more diverse TCR usage observed for HIV-2-specific CD8(+) T cells was associated with an enhanced potential for CD8 expansion and IFN-gamma production on cross-recognition of variant epitopes. Our data suggest a mechanism that could account for any possible cross-protection that may be mediated by HIV-2-specific CD8(+) T cells against HIV-1 infection. Furthermore, they have implications for HIV vaccine development, demonstrating an association between a polyclonal, virus-specific CD8(+) T cell response and an enhanced capacity to tolerate substitutions within T cell epitopes.

Type

Journal article

Journal

J Immunol

Publication Date

01/07/2003

Volume

171

Pages

307 - 316

Keywords

Amino Acid Sequence, Amino Acid Substitution, Antigen Presentation, CD8-Positive T-Lymphocytes, Cell Division, Cell Line, Clone Cells, Epitopes, T-Lymphocyte, Gene Products, gag, Gene Rearrangement, T-Lymphocyte, HIV Infections, HIV-1, HIV-2, HLA-A2 Antigen, Humans, Molecular Sequence Data, Peptide Fragments, Receptors, Antigen, T-Cell, alpha-beta