title: Differences in the expressed HLA class I alleles effect the differential clustering of HIV type 1-specific T cell responses in infected Chinese and caucasians.
abstract: China is a region of the world with a rapidly spreading HIV-1 epidemic. Studies providing insights into HIV-1 pathogenesis in infected Chinese are urgently needed to support the design and testing of an effective HIV-1 vaccine for this population. HIV-1-specific T cell responses were characterized in 32 HIV-1-infected individuals of Chinese origin and compared to 34 infected caucasians using 410 overlapping peptides spanning the entire HIV-1 clade B consensus sequence in an IFN-gamma ELISpot assay. All HIV-1 proteins were targeted with similar frequency in both populations and all study subjects recognized at least one overlapping peptide. HIV-1-specific T cell responses clustered in seven different regions of the HIV-1 genome in the Chinese cohort and in nine different regions in the caucasian cohort. The dominant HLA class I alleles expressed in the two populations differed significantly, and differences in epitope clustering pattern were shown to be influenced by differences in class I alleles that restrict immunodominant epitopes. These studies demonstrate that the clustering of HIV-1-specific T cell responses is influenced by the genetic HLA class I background in the study populations. The design and testing of candidate vaccines to fight the rapidly growing HIV-1 epidemic must therefore take the HLA genetics of the population into account as specific regions of the virus can be expected to be differentially targeted in ethnically diverse populations.
authors.affiliation: Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02129, USA.
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.forename: Marylyn M
authors.initials: MM
authors.lastname: Addo
authors.forename: Beth A
authors.initials: BA
authors.lastname: Perkins
authors.forename: Feili
authors.initials: F
authors.lastname: Wej
authors.forename: Almas
authors.initials: A
authors.lastname: Rathod
authors.forename: Shaun C
authors.initials: SC
authors.lastname: Geer
authors.forename: Mark
authors.initials: M
authors.lastname: Parta
authors.forename: Daniel
authors.initials: D
authors.lastname: Cohen
authors.forename: David R
authors.initials: DR
authors.lastname: Stone
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Russell
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Tanzi
authors.forename: Shan
authors.initials: S
authors.lastname: Mei
authors.forename: Alysse G
authors.initials: AG
authors.lastname: Wurcel
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Mathias
authors.initials: M
authors.lastname: Lichterfeld
authors.forename: Laura
authors.initials: L
authors.lastname: Heath
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Francesco
authors.initials: F
authors.lastname: Marincola
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Todd
authors.initials: T
authors.lastname: Allen
authors.forename: Yunzhen
authors.initials: Y
authors.lastname: Cao
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D002681:China; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005006:Ethnicity; D005805:Genes, MHC Class I; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*; D044465:White People