title: Immunodominant HIV-1-specific HLA-B- and HLA-C-restricted CD8+ T cells do not differ in polyfunctionality.
abstract: HIV-1 specific HLA-B-restricted CD8+ T cell responses differ from HLA-C-restricted responses in antiviral effectiveness. To investigate possible reasons for these differences, we characterized the frequency and polyfunctionality of immmunodominant HLA-B*57/B5801- and HLA-Cw*07-restricted CD8+ T cells occurring concurrently in nine study subjects assessing IFN-gamma, TNF-alpha, IL-2, MIP-1beta, and CD107a by flow cytometry and analyzed sequence variation in targeted epitopes. HLA-B*57/5801 and HLA-Cw*07 restricted CD8+ T cells did not differ significantly in polyfunctionality (p=0.84). Possession of three or more functions correlated positively with CD4+ T cell counts (r=0.85; p=0.006) and monofunctional CD8+ T cells inversely correlated with CD4 cell counts (r=-0.79; p=0.05). There were no differences in polyfunctionality of CD8+ T cells specific to wildtype versus mutated epitopes. These results suggest that loss of polyfunctionality and increase in monofunctional HIV-1-specific CD8+ T cells are associated with disease progression independent of restricting HLA allele. Furthermore, sequence variation does not appear to significantly impact CD8+ T cell polyfunctionality in chronic HIV-1 infection.
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Nompumelelo
authors.initials: N
authors.lastname: Mkhwanazi
authors.forename: Christina F
authors.initials: CF
authors.lastname: Thobakgale
authors.forename: Mary
authors.initials: M
authors.lastname: van der Stok
authors.forename: Shabashini
authors.initials: S
authors.lastname: Reddy
authors.forename: Zenele
authors.initials: Z
authors.lastname: Mncube
authors.forename: Fundisiwe
authors.initials: F
authors.lastname: Chonco
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002908:Chronic Disease; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D015235:HLA-B Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D019562:Viral Load
chemical_list: D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C500126:HLA-B*58:01 antigen; C103707:HLA-B57 antigen; D015236:HLA-C Antigens; D016056:Immunodominant Epitopes