Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection.

Journal article

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.

Authors: Lopes, A; Jaye, A; Dorrell, L; Sabally, S; Alabi, A

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 171
• Issue: 1
• Pages: 307-316
• Publication date: 2003-07-01
• DOI: 10.4049/jimmunol.171.1.307
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Peptide Fragments; Epitopes, T-Lymphocyte; HIV-1; Gene Products, gag; CD8-Positive T-Lymphocytes; Clone Cells; Cell Line; Gene Rearrangement, T-Lymphocyte; Amino Acid Substitution; HIV Infections; HLA-A2 Antigen; HIV-2; Antigen Presentation; Molecular Sequence Data; Receptors, Antigen, T-Cell, alpha-beta; Cell Division; Humans; Amino Acid Sequence