title: HLA-B63 presents HLA-B57/B58-restricted cytotoxic T-lymphocyte epitopes and is associated with low human immunodeficiency virus load.
abstract: Several HLA class I alleles have been associated with slow human immunodeficiency virus (HIV) disease progression, supporting the important role HLA class I-restricted cytotoxic T lymphocytes (CTL) play in controlling HIV infection. HLA-B63, the serological marker for the closely related HLA-B*1516 and HLA-B*1517 alleles, shares the epitope binding motif of HLA-B57 and HLA-B58, two alleles that have been associated with slow HIV disease progression. We investigated whether HIV-infected individuals who express HLA-B63 generate CTL responses that are comparable in breadth and specificity to those of HLA-B57/58-positive subjects and whether HLA-B63-positive individuals would also present with lower viral set points than the general population. The data show that HLA-B63-positive individuals indeed mounted responses to previously identified HLA-B57-restricted epitopes as well as towards novel, HLA-B63-restricted CTL targets that, in turn, can be presented by HLA-B57 and HLA-B58. HLA-B63-positive subjects generated these responses early in acute HIV infection and were able to control HIV replication in the absence of antiretroviral treatment with a median viral load of 3,280 RNA copies/ml. The data support an important role of the presented epitope in mediating relative control of HIV replication and help to better define immune correlates of controlled HIV infection.
authors.affiliation: Partners AIDS Research Center, Massachusetts General Hospital, No. 5214, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Sharon
authors.initials: S
authors.lastname: Adams
authors.forename: Photini
authors.initials: P
authors.lastname: Kiepiela
authors.forename: Caitlyn H
authors.initials: CH
authors.lastname: Linde
authors.forename: Hannah S
authors.initials: HS
authors.lastname: Hewitt
authors.forename: Mathias
authors.initials: M
authors.lastname: Lichterfeld
authors.forename: Kaori
authors.initials: K
authors.lastname: Sango
authors.forename: Nancy V
authors.initials: NV
authors.lastname: Brown
authors.forename: Eunice
authors.initials: E
authors.lastname: Pae
authors.forename: Alysse G
authors.initials: AG
authors.lastname: Wurcel
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Feeney
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Timothy
authors.initials: T
authors.lastname: Roach
authors.forename: M Anne
authors.initials: MA
authors.lastname: St John
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Eric
authors.initials: E
authors.lastname: Rosenberg
authors.forename: Bette
authors.initials: B
authors.lastname: Korber
authors.forename: Francesco
authors.initials: F
authors.lastname: Marincola
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D018984:Epitopes, T-Lymphocyte; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load
chemical_list: D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C103707:HLA-B57 antigen