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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dc.contributor.author Malhotra, Uma en_US
dc.contributor.author Holte, Sarah en_US
dc.contributor.author Dutta, Sujay en_US
dc.contributor.author Berrey, M. Michelle en_US
dc.contributor.author Delpit, Elizabeth en_US
dc.contributor.author Koelle, David M. en_US
dc.contributor.author Sette, Alessandro en_US
dc.contributor.author Corey, Lawrence en_US
dc.contributor.author McElrath, M. Juliana en_US
dc.date.accessioned 2010-04-21T15:57:14Z
dc.date.available 2010-04-21T15:57:14Z
dc.date.issued 2001-02-15 en_US
dc.identifier.citation Malhotra U, Holte S, Dutta S, et al. Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment. J Clin Invest. 2001;107(4):505-517. en_US
dc.identifier.other 10.1172/JCI11275 en_US
dc.identifier.uri http://www.jci.org/articles/view/11275 en_US
dc.identifier.uri http://hdl.handle.net/1773/15784
dc.description.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. en_US
dc.description.sponsorship NIH grants AI-41535, AI-01411, AI-30731, POICA-76466, and AI-27757. en_US
dc.language.iso en_US en_US
dc.title Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment en_US


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