title: Relative contribution of HIV-specific functional lymphocyte subsets restricted by protective and non-protective HLA alleles.
abstract: Expression of major histocompatibility complex (MHC) class I alleles such as B*57 and B*27 are associated with slow HIV disease progression. HIV-specific immune responses in slow progressors (SP) are characterized by a poly-functional profile. We previously observed within infected subjects that HIV peptide-specific responses could differ from each other in their functional composition. We investigate here whether responses restricted by MHC class I alleles associated with slow disease progression have a more poly-functional profile than responses restricted by other alleles. We stimulated peripheral blood mononuclear cells (PBMCs) isolated from 36 chronically HIV-infected individuals with a panel of optimal peptides restricted by the HLA alleles expressed by each subject, and assessed the contribution of single IL-2-, single IFN-γ-, and IFN-γ/IL-2-secreting lymphocytes to the total response measured using a dual color ELISPOT assay. The contribution of functional subsets to responses restricted by HLA B*57/B*27 was similar in SP and progressors. For responses restricted by other MHC class I alleles, dual IFN-γ/IL-2-secreting lymphocytes contributed significantly more to the total response in SP than progressors. Within SP subjects, peptides restricted by both B*57/B*27 and other alleles stimulated responses with similar functional profiles. In progressors, peptides restricted by B*57/B*27 stimulated responses composed of a significantly greater proportion of IFN-γ/IL-2-secreting cells than peptides restricted by other alleles. Within progressors, the contribution of IFN-γ/IL-2-secreting lymphocytes was greater to epitopes restricted by protective HLA alleles compared with responses restricted by other alleles. HLA haplotypes influence the relative functional composition of HIV-specific responses.
authors.affiliation: National Immune Monitoring Laboratory (NIML), Genome Québec, Montreal, Québec, Canada.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Peretz
authors.forename: Olivia
authors.initials: O
authors.lastname: Marra
authors.forename: Réjean
authors.initials: R
authors.lastname: Thomas
authors.forename: Danielle
authors.initials: D
authors.lastname: Legault
authors.forename: Pierre
authors.initials: P
authors.lastname: Côté
authors.forename: Mohamed-Rachid
authors.initials: MR
authors.lastname: Boulassel
authors.forename: Danielle
authors.initials: D
authors.lastname: Rouleau
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sékaly
authors.forename: Christos M
authors.initials: CM
authors.lastname: Tsoukas
authors.forename: Cécile
authors.initials: C
authors.lastname: Tremblay
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Bernard
mesh_terms: D000483:Alleles; D000956:Antigens, Viral / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D020276:HIV Long-Term Survivors; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D006680:HLA Antigens