Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment

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Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment

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Title: Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment
Author: Malhotra, Uma; Holte, Sarah; Dutta, Sujay; Berrey, M. Michelle; Delpit, Elizabeth; Koelle, David M.; Sette, Alessandro; Corey, Lawrence; McElrath, M. Juliana
Abstract: 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.
URI: http://www.jci.org/articles/view/11275
http://hdl.handle.net/1773/15784

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