HLA-B63 presents HLA-B57/B58-restricted cytotoxic T-lymphocyte epitopes and is associated with low human immunodeficiency virus load.

Abstract

Several HLA class I alleles have been associated with slow human immunodeficiency virus (HIV) disease progression, supporting the important role HLA class I-restricted cytotoxic T lymphocytes (CTL) play in controlling HIV infection. HLA-B63, the serological marker for the closely related HLA-B*1516 and HLA-B*1517 alleles, shares the epitope binding motif of HLA-B57 and HLA-B58, two alleles that have been associated with slow HIV disease progression. We investigated whether HIV-infected individuals who express HLA-B63 generate CTL responses that are comparable in breadth and specificity to those of HLA-B57/58-positive subjects and whether HLA-B63-positive individuals would also present with lower viral set points than the general population. The data show that HLA-B63-positive individuals indeed mounted responses to previously identified HLA-B57-restricted epitopes as well as towards novel, HLA-B63-restricted CTL targets that, in turn, can be presented by HLA-B57 and HLA-B58. HLA-B63-positive subjects generated these responses early in acute HIV infection and were able to control HIV replication in the absence of antiretroviral treatment with a median viral load of 3,280 RNA copies/ml. The data support an important role of the presented epitope in mediating relative control of HIV replication and help to better define immune correlates of controlled HIV infection.

• Authors: Nicole Frahm, Sharon Adams, Photini Kiepiela, Caitlyn H Linde, Hannah S Hewitt, Mathias Lichterfeld, Kaori Sango, Nancy V Brown, Eunice Pae, Alysse G Wurcel, Marcus Altfeld, Margaret E Feeney, Todd M Allen, Timothy Roach, M Anne St John, Eric S Daar, Eric Rosenberg, Bette Korber, Francesco Marincola, Bruce D Walker, Philip J R Goulder, Christian Brander
• Journal: Journal of virology (J Virol) Vol. 79 Issue 16 Pg. 10218-25 (Aug 2005) ISSN: 0022-538X [Print] United States
• PMID: 16051815 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epitopes, T-Lymphocyte
• HLA-B Antigens
• HLA-B57 antigen

Topics

• Amino Acid Sequence
• Antigen Presentation
• Epitopes, T-Lymphocyte
• HIV Infections (immunology, virology)
• HLA-B Antigens (immunology)
• Humans
• Molecular Sequence Data
• T-Lymphocytes, Cytotoxic (immunology)
• Viral Load