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

A. Ross Lopes, Assan Jaye, Lucy Dorrell, Sehu Sabally, Abraham Alabi, Nicola A. Jones, Darren R. Flower, Anne de Groot, Phillipa Newton, R. Monica Lascar, Ian Williams, Hilton Whittle, Antonio Bertoletti, Persephone Borrow, Mala K. Maini

Research output: Contribution to journalArticle

Abstract

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- 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.
Original languageEnglish
Pages (from-to)307-316
Number of pages10
JournalJournal of Immunology
Volume171
Issue number1
DOIs
Publication statusPublished - 1 Jul 2003

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HIV-2
HIV Infections
HIV-1
T-Lymphocytes
Epitopes
Cross Protection
Viruses
HLA-A2 Antigen
AIDS Vaccines
T-Lymphocyte Epitopes
Amino Acid Substitution
Infection Control

Cite this

Lopes, A. R., Jaye, A., Dorrell, L., Sabally, S., Alabi, A., Jones, N. A., ... Maini, M. K. (2003). Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection. Journal of Immunology, 171(1), 307-316. https://doi.org/10.4049/jimmunol.171.1.307
Lopes, A. Ross ; Jaye, Assan ; Dorrell, Lucy ; Sabally, Sehu ; Alabi, Abraham ; Jones, Nicola A. ; Flower, Darren R. ; de Groot, Anne ; Newton, Phillipa ; Lascar, R. Monica ; Williams, Ian ; Whittle, Hilton ; Bertoletti, Antonio ; Borrow, Persephone ; Maini, Mala K. / Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection. In: Journal of Immunology. 2003 ; Vol. 171, No. 1. pp. 307-316.
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Lopes, AR, Jaye, A, Dorrell, L, Sabally, S, Alabi, A, Jones, NA, Flower, DR, de Groot, A, Newton, P, Lascar, RM, Williams, I, Whittle, H, Bertoletti, A, Borrow, P & Maini, MK 2003, 'Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection', Journal of Immunology, vol. 171, no. 1, pp. 307-316. https://doi.org/10.4049/jimmunol.171.1.307

Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection. / Lopes, A. Ross; Jaye, Assan; Dorrell, Lucy; Sabally, Sehu; Alabi, Abraham; Jones, Nicola A.; Flower, Darren R.; de Groot, Anne; Newton, Phillipa; Lascar, R. Monica; Williams, Ian; Whittle, Hilton; Bertoletti, Antonio; Borrow, Persephone; Maini, Mala K.

In: Journal of Immunology, Vol. 171, No. 1, 01.07.2003, p. 307-316.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection

AU - Lopes, A. Ross

AU - Jaye, Assan

AU - Dorrell, Lucy

AU - Sabally, Sehu

AU - Alabi, Abraham

AU - Jones, Nicola A.

AU - Flower, Darren R.

AU - de Groot, Anne

AU - Newton, Phillipa

AU - Lascar, R. Monica

AU - Williams, Ian

AU - Whittle, Hilton

AU - Bertoletti, Antonio

AU - Borrow, Persephone

AU - Maini, Mala K.

PY - 2003/7/1

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N2 - 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- 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.

AB - 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- 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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DO - 10.4049/jimmunol.171.1.307

M3 - Article

VL - 171

SP - 307

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JO - Journal of Immunology

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