Association of HLA-DRB1-restricted CD4+ T cell responses with HIV immune control
| Autor: | Srinika Ranasinghe, Madelene Lindqvist, Sam Cutler, Michael Flanders, Steven G. Deeks, Damien Z. Soghoian, Hendrik Streeck, Alessandro Sette, Galit Alter, Ying Qi, Bjorn D. Kuhl, Richard Lu, Gregory Kranias, Isaiah Davis, Mary Carrington, Bruce D. Walker, John Sidney, Xiaojiang Gao |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
musculoskeletal diseases
CD4-Positive T-Lymphocytes T cell Viremia HIV Infections Human leukocyte antigen Biology Virus Replication General Biochemistry Genetics and Molecular Biology Article Cohort Studies 03 medical and health sciences 0302 clinical medicine Gene Frequency immune system diseases medicine Humans Avidity Genetic Predisposition to Disease Allele skin and connective tissue diseases HLA-DRB1 Alleles Cells Cultured Genetic Association Studies 030304 developmental biology Disease Resistance 0303 health sciences virus diseases General Medicine Viral Load medicine.disease Virology 3. Good health medicine.anatomical_structure Viral replication Immunology HIV-1 Viral load 030215 immunology HLA-DRB1 Chains |
| Zdroj: | Nature medicine |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | The contribution of HLA class II-restricted CD4+ T cell responses to HIV immune control is poorly defined. Here, we delineated novel peptide-DRB1 restrictions in functional assays and analyzed the host genetic effects of HLA-DRB1 alleles on HIV viremia in a large cohort of HIV controllers and progressors (n=1085). We found distinct stratifications in the effect of HLA-DRB1 alleles on HIV viremia, with DRB1*15:02 significantly associated with low viremia (P=0.003, q=0.04) and DRB1*03:01 significantly associated with high viremia (P=0.004, q=0.04). Interestingly, a sub-group of HLA-DRB1 alleles linked with low viremia showed the ability to promiscuously present a larger breadth of peptides with lower functional avidity when compared to HLA-DRB1 alleles linked with high viremia (p=0.018). Our data provide systematic evidence that HLA-DRB1 allele expression significantly impacts the durable control of HIV replication, an effect that appears to be mediated primarily by the protein-specificity of HIV-specific CD4+ T cell responses to Gag and Nef. |
| Databáze: | OpenAIRE |
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