HIV-1–infected patients treated early with combination antiretrovirals respond favorably, but not all maintain viral suppression and improved HIV-specific Th function. To understand if genetic factors contribute to this variation, we prospectively evaluated over 18 months 21 early-treated patients stratified by alleles of class II haplotypes. All seven subjects with the DRB1*13-DQB1*06 haplotype, but only 21% of other subjects, maintained virus suppression at every posttreatment measurement. Following HIV-1 p24 antigen stimulation, PBMCs from patients with this haplotype demonstrated higher mean lymphoproliferation and IFN-γ secretion than did cells from patients with other haplotypes. Two DRB1*13-restricted Gag epitope regions were identified, a promiscuous one that bound its putative restriction element with nanomolar affinity, and another that mapped to a highly conserved region. These findings suggest that class II molecules, particularly the DRB1*13 haplotype, have an important impact on virologic and immunologic responses. The advantage of the haplotype may relate to selection of key HIV-1 Th1 epitopes in highly conserved regions with avid binding to class II molecules. Eliciting responses to the promiscuous epitope region may be beneficial in vaccine strategies.
Uma Malhotra, Sarah Holte, Sujay Dutta, M. Michelle Berrey, Elizabeth Delpit, David M. Koelle, Alessandro Sette, Lawrence Corey, M. Juliana McElrath
Title and authors | Publication | Year |
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Human leukocyte antigens and HIV type 1 viral load in early and chronic infection: predominance of evolving relationships
J Tang, R Malhotra, W Song, I Brill, L Hu, PK Farmer, J Mulenga, S Allen, E Hunter, RA Kaslow |
PloS one | 2010 |
Induction of Immunity to Human Immunodeficiency Virus Type-1 by Vaccination
MJ McElrath, BF Haynes |
Immunity | 2010 |
HIV Controllers with HLA-DRB1*13 and HLA-DQB1*06 Alleles Have Strong, Polyfunctional Mucosal CD4 + T-Cell Responses
AL Ferre, PW Hunt, DH McConnell, MM Morris, JC Garcia, RB Pollard, HF Yee, JN Martin, SG Deeks, BL Shacklett |
Journal of virology | 2010 |
HIV Controller CD4+ T Cells Respond to Minimal Amounts of Gag Antigen Due to High TCR Avidity
Vingert B, Perez-Patrigeon S, Jeannin P, Lambotte O, Boufassa F, Lemaître F, Kwok WW, Theodorou I, Delfraissy JF, Thèze J, Chakrabarti LA |
PLoS pathogens | 2010 |