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HLA-B63 Presents HLA-B57/B58-Restricted Cytotoxic T-Lymphocyte Epitopes and Is Associated with Low Human Immunodeficiency Virus Load

2005; American Society for Microbiology; Volume: 79; Issue: 16 Linguagem: Inglês

10.1128/jvi.79.16.10218-10225.2005

1098-5514

Nicole Frahm, Sharon Adams, Photini Kiepiela, Caitlyn 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 M. Marincola, Bruce D. Walker, Philip Goulder, Christian Brander,

T-cell and B-cell Immunology

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.