title: Association of HLA-DRB1-restricted CD4⁺ T cell responses with HIV immune control.
abstract: The contribution of HLA class II-restricted CD4(+) T cell responses to HIV immune control is poorly defined. Here, we delineated previously uncharacterized 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. We found distinct stratifications in the effect of HLA-DRB1 alleles on HIV viremia, with HLA-DRB1*15:02 significantly associated with low viremia and HLA-DRB1*03:01 significantly associated with high viremia. Notably, a subgroup of HLA-DRB1 variants linked with low viremia showed the ability to promiscuously present a larger breadth of peptides with lower functional avidity when compared to HLA-DRB1 variants linked with high viremia. Our data provide systematic evidence that HLA-DRB1 variant expression has a considerable impact on the control of HIV replication, an effect that seems to be mediated primarily by the protein specificity of CD4(+) T cell responses to HIV Gag and Nef.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Srinika
authors.initials: S
authors.lastname: Ranasinghe
authors.forename: Sam
authors.initials: S
authors.lastname: Cutler
authors.forename: Isaiah
authors.initials: I
authors.lastname: Davis
authors.forename: Richard
authors.initials: R
authors.lastname: Lu
authors.forename: Damien Z
authors.initials: DZ
authors.lastname: Soghoian
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Gregory
authors.initials: G
authors.lastname: Kranias
authors.forename: Michael D
authors.initials: MD
authors.lastname: Flanders
authors.forename: Madelene
authors.initials: M
authors.lastname: Lindqvist
authors.forename: Bjorn
authors.initials: B
authors.lastname: Kuhl
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
mesh_terms: D000483:Alleles; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D015331:Cohort Studies; D060467:Disease Resistance / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019562:Viral Load / Q000235:genetics / Q000502:physiology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D059811:HLA-DRB1 Chains