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The Journal of Immunology, 2003, 171: 307-316.
Copyright © 2003 by The American Association of Immunologists

Greater CD8+ TCR Heterogeneity and Functional Flexibility in HIV-2 Compared to HIV-1 Infection1

A. Ross Lopes*,{dagger}, Assan Jaye{ddagger}, Lucy Dorrell{ddagger},§, Sehu Sabally{ddagger}, Abraham Alabi{ddagger}, Nicola A. Jones, Darren R. Flower, Anne De Groot||, Phillipa Newton{dagger}, R. Monica Lascar{dagger}, Ian Williams{dagger}, Hilton Whittle{ddagger}, Antonio Bertoletti*, Persephone Borrow and Mala K. Maini2,*,{dagger}

* Institute of Hepatology and {dagger} Department of Sexually Transmitted Diseases, University College London, London, United Kingdom; {ddagger} MRC Laboratories, Fajara, The Gambia, Africa; § Medical Research Council Human Immunology Group, John Radcliffe Hospital, Oxford, United Kingdom; The Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom; and || Tuberculosis/HIV Research Laboratory, Brown University, Providence RI 02912

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.




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