Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment
| Autor: | Sarah Holte, Uma Malhotra, Sujay Dutta, Alessandro Sette, Lawrence Corey, M. Michelle Berrey, M. Juliana McElrath, Elizabeth Delpit, David M. Koelle |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Cellular immunity Anti-HIV Agents Genes MHC Class II Molecular Sequence Data Gene Products gag Biology Lymphocyte Activation Peripheral blood mononuclear cell Virus Epitope HLA-DQ Antigens HLA-DQ beta-Chains Humans Amino Acid Sequence Prospective Studies Allele Alleles HLA-DR Antigen Acquired Immunodeficiency Syndrome HLA-DQ Antigen Haplotype HLA-DR Antigens General Medicine Virology CD4 Lymphocyte Count Haplotypes Immunology HIV-1 Commentary Cytokines Drug Therapy Combination HLA-DRB1 Chains |
| Zdroj: | Journal of Clinical Investigation. 107:505-517 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci11275 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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