title: Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes.
abstract: Despite limited data supporting the superiority of dominant over subdominant responses, immunodominant epitopes represent the preferred vaccine candidates. To address the function of subdominant responses in human immunodeficiency virus infection, we analyzed cytotoxic T lymphocyte responses restricted by HLA-B*1503, a rare allele in a cohort infected with clade B, although common in one infected with clade C. HLA-B*1503 was associated with reduced viral loads in the clade B cohort but not the clade C cohort, although both shared the immunodominant response. Clade B viral control was associated with responses to several subdominant cytotoxic T lymphocyte epitopes, whereas their clade C variants were less well recognized. These data suggest that subdominant responses can contribute to in vivo viral control and that high HLA allele frequencies may drive the elimination of subdominant yet effective epitopes from circulating viral populations.
authors.affiliation: Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Photini
authors.initials: P
authors.lastname: Kiepiela
authors.forename: Sharon
authors.initials: S
authors.lastname: Adams
authors.forename: Caitlyn H
authors.initials: CH
authors.lastname: Linde
authors.forename: Hannah S
authors.initials: HS
authors.lastname: Hewitt
authors.forename: Kaori
authors.initials: K
authors.lastname: Sango
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Feeney
authors.forename: Marylyn M
authors.initials: MM
authors.lastname: Addo
authors.forename: Mathias
authors.initials: M
authors.lastname: Lichterfeld
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Lahaie
authors.forename: Eunice
authors.initials: E
authors.lastname: Pae
authors.forename: Alysse G
authors.initials: AG
authors.lastname: Wurcel
authors.forename: Timothy
authors.initials: T
authors.lastname: Roach
authors.forename: M Anne
authors.initials: MA
authors.lastname: St John
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Corey
authors.initials: C
authors.lastname: Moore
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D015331:Cohort Studies; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics; D014644:Genetic Variation; D015488:HIV Antigens / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D015235:HLA-B Antigens / Q000235:genetics; D059910:HLA-B15 Antigen; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015488:HIV Antigens; D015235:HLA-B Antigens; D059910:HLA-B15 Antigen; D016056:Immunodominant Epitopes