title: Human immunodeficiency virus type 1 (HIV-1)-specific CD8+-T-cell responses for groups of HIV-1-infected individuals with different HLA-B*35 genotypes.
abstract: Human immunodeficiency virus type 1 (HIV-1)-infected individuals with HLA-B*35 allelic variants B*3502/3503/3504/5301 (B*35-Px) progress more rapidly to AIDS than do those with B*3501 (B*35-PY). The mechanisms responsible for this phenomenon are not clear. To examine whether cellular immune responses may differ according to HLA-B*35 genotype, we quantified HIV-1-specific CD8(+)-T-cell (CTL) responses using an intracellular cytokine-staining assay with specimens from 32 HIV-1-positive individuals who have B*35 alleles. Among them, 75% had CTL responses to Pol, 69% had CTL responses to Gag, 50% had CTL responses to Nef, and 41% had CTL responses to Env. The overall magnitude of CTL responses did not differ between patients bearing B*35-Px genotypes and those bearing B*35-PY genotypes. A higher percentage of Gag-specific CTL was associated with lower HIV-1 RNA levels (P = 0.009) in individuals with B*35-PY. A negative association between CTL activity for each of the four HIV antigens and viral load was observed among individuals with B*35-PY, and the association reached significance for Gag. No significant relationship between CTL activity and viral load was observed in the B*35-Px group. The relationship between total CTL activity and HIV RNA among B*35-Px carriers differed significantly from that among B*35-PY carriers (P < 0.05). The data are consistent with the hypothesis that higher levels of virus-specific CTL contribute to protection against HIV disease progression in infected individuals with B*35-PY, but not in those with B*35-Px.
authors.affiliation: Infectious Disease Unit, University of Rochester Medical Center, 601 Elmwood Avenue, Box 689, Rochester, NY 14642, USA. Xia_Jin@URMC.Rochester.edu
authors.forename: Xia
authors.initials: X
authors.lastname: Jin
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: Murugappan
authors.initials: M
authors.lastname: Ramanathan
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Deschenes
authors.forename: George W
authors.initials: GW
authors.lastname: Nelson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
authors.forename: Thomas R
authors.initials: TR
authors.lastname: O'Brien
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D018450:Disease Progression; D005838:Genotype; D015497:HIV-1 / Q000276:immunology*; D015797:HLA-B35 Antigen / Q000235:genetics*; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load
chemical_list: D015797:HLA-B35 Antigen