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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Strong TCR conservation and altered T cell cross-reactivity characterize a B*57-restricted immune response in HIV-1 infection
Journal of Immunology, Volume 177, No. 6, Year 2006
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Description
HLA-B*57 is associated with slower disease progression to AIDS, and CD8+ T cell responses to B*57-restricted epitopes are thought to contribute to this protective effect. In this study, we evaluate the B*57-restricted p24 KAFSPEVIPMF (KF11) immune response which is immunodominant during chronic infection. Previously, we observed that the KF11 clade variants KGFNPEVIPMF [A2G,S4N] and KAFNPEIIMPF [S4N,V7I], sharing a position 4 mutation, are differentially recognized by KF11-specific T cells. By combining structural and cellular studies, we now demonstrate that the KF11 and [A2G,S4N] epitopes induce distinct functional responses in [A2G,S4N] and KF11-specific T cells, respectively, despite minimal structural differences between the individual B*57-peptide complexes. Recently, we also elucidated the highly distinct structure of KF11 in complex with B*5703, and have now characterized the CD8+ T cell repertoire recognizing this epitope. We now report striking features of TCR conservation both in terms of TCR Vα and Vβ chain usage, and throughout the hypervariable region. Collectively, our findings highlight unusual features of the B*5701/B*5703-KF11-specific immune responses which could influence disease progression and that might be important to consider when designing future vaccine regimens. Copyright © 2006 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Gillespie, Geraldine M.A.
United Kingdom, Oxford
John Radcliffe Hospital
Stewart-Jones, Guillaume B.E.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Rengasamy, Jaya
United Kingdom, Oxford
John Radcliffe Hospital
Beattie, Tara S.H.
United Kingdom, Oxford
John Radcliffe Hospital
Bwayo, Job J.
Kenya, Nairobi
University of Nairobi
Plummer, Francis Allan
Canada, Winnipeg
University of Manitoba
Kaul, Rupert
Canada, Toronto
University of Toronto
McMichael, Andrew James
United Kingdom, Oxford
John Radcliffe Hospital
Easterbrook, Philippa Jane
United Kingdom, London
King's College London
Deng, Tao
United Kingdom, Oxford
John Radcliffe Hospital
Jones, Edith Yvonne
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Rowland-Jones, Sarah Louise
United Kingdom, Oxford
John Radcliffe Hospital
Statistics
Citations: 62
Authors: 12
Affiliations: 6
Identifiers
Doi:
10.4049/jimmunol.177.6.3893
ISSN:
00221767
Research Areas
Cancer
Infectious Diseases