HLA-B63 presents HLA-B57/B58-restricted cytotoxic T-lymphocyte epitopes and is associated with low human immunodeficiency virus load - PubMed (original) (raw)

. 2005 Aug;79(16):10218-25.

doi: 10.1128/JVI.79.16.10218-10225.2005.

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

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

Nicole Frahm et al. J Virol. 2005 Aug.

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.

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Figures

FIG. 1.

FIG. 1.

Epitope fine mapping of HLA-B57-restricted CTL epitopes in HLA-B63-positive subjects. Responses to serially 10-fold-diluted, truncated peptides in ELISPOT are shown for epitopes KF11 (a), KY10 (b), and IW9 (c, d). The optimal epitope was defined as the shortest epitope inducing the strongest response at the lowest concentration (4). Captions include the subjects and their respective HLA types.

FIG. 2.

FIG. 2.

Epitope fine mapping of HLA-B63-restricted CTL epitopes. Responses to serially 10-fold-diluted, truncated peptides in ELISPOT are shown for epitopes LL9 (OLP 85) (a, b), RY11 (OLP 11) (c), YY9 (OLP 84) (d), FF9 (OLP 23) (e), and KV8 (OLP 162) (f). The optimal epitope was defined as the shortest epitope inducing the strongest response at the lowest concentration (4). Captions include the subjects and their respective HLA types, and used truncations are shown in the legend.

FIG. 3.

FIG. 3.

Magnitude of responses during acute infection. The relative magnitude of responses restricted by HLA-B63 or other alleles is shown for subjects B19 (a) and B20 (b), indicating the preferential targeting of HLA-B63 responses early in infection.

FIG. 4.

FIG. 4.

Viral loads of HLA-B63-positive subjects are compared to the remainder of the cohorts (including B57/58-positive subjects). Viral set points are shown for 19 untreated, chronically HIV clade B- or C-infected, HLA-B63-positive individuals (large diamonds) and 576 untreated, HLA-B63-negative clade B- and clade C-infected individuals (small diamonds). Medians are shown as horizontal black lines.

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