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

被引:97
作者
Malhotra, U
Holte, S
Dutta, S
Berrey, MM
Delpit, E
Koelle, DM
Sette, A
Corey, L
McElrath, MJ
机构
[1] Epimmune, San Diego, CA USA
[2] Univ Washington, Sch Med, Dept Lab Med, Seattle, WA USA
[3] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Biostat, Seattle, WA 98104 USA
[4] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA
[5] Fred Hutchinson Canc Res Ctr, Div Clin Res, Program Infect Dis, Seattle, WA 98109 USA
基金
英国惠康基金;
关键词
D O I
10.1172/JCI11275
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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-gamma 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.
引用
收藏
页码:505 / 517
页数:13
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