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Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment.
Title | Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment. |
Publication Type | Journal Article |
Year of Publication | 2001 |
Authors | Malhotra, U, Holte, S, Dutta, S, Berrey, MM, Delpit, E, Koelle, DM, Sette, A, Corey, L, McElrath, MJ |
Journal | J Clin Invest |
Volume | 107 |
Issue | 4 |
Pagination | 505-17 |
Date Published | 2001 Feb |
ISSN | 0021-9738 |
Keywords | Acquired Immunodeficiency Syndrome, Adult, Alleles, Amino Acid Sequence, Anti-HIV Agents, CD4 Lymphocyte Count, Cytokines, Drug Therapy, Combination, Gene Products, gag, Genes, MHC Class II, Haplotypes, HIV-1, HLA-DQ Antigens, HLA-DQ beta-Chains, HLA-DR Antigens, HLA-DRB1 Chains, Humans, Lymphocyte Activation, Male, Molecular Sequence Data, Prospective Studies |
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-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. |
DOI | 10.1172/JCI11275 |
Alternate Journal | J. Clin. Invest. |
PubMed ID | 11181650 |