Identification and characterization of HLA-A*3303-restricted, HIV type 1 Pol- and Gag-derived cytotoxic T cell epitopes

AIDS Res Hum Retroviruses. 2003 Jun;19(6):503-10. doi: 10.1089/088922203766774559.

Abstract

HLA-A*3303 is one of the common HLA alleles in East and Southeast Asia. Identification of HLA-A*3303-restricted HIV-1 cytotoxic T lymphocyte (CTL) epitopes is therefore required to investigate the immunopathogenesis of AIDS and vaccine development in these areas, where AIDS is rapidly expanding. We attempted to identify HLA-A*3303-restricted CTL epitopes derived from relatively conserved proteins Pol, Gag, and Nef of HIV-1 clade B, using reverse immunogenetics. Ninety-nine 8-mer to 11-mer peptides corresponding to the HLA-A*3303-binding peptide motif were selected from the HIV-1 SF2 sequence. Fifty-two of these 99 peptides bound to HLA-A*3303. Six of these binding peptides induced peptide-specific CTLs in PBMCs from at least one of two HIV-1-seropositive individuals. CTL clones specific for three Pol peptides and one Gag peptide killed HLA-A*3303-restricted target cells infected with HIV-1 recombinant vaccinia, indicating that these peptides were naturally processed HLA-A*3303-restricted CTL epitopes. SF2-Pol 594-602 (FYVDGAANR) and SF2-Gag 144-152 (MVHQAISPR) induced specific CTLs in 5 and 4 of 10 chronically HIV-1-infected individuals, respectively, whereas SF2-Pol 60-70 (TLWQRPLVTIR) and SF2-Pol 934-943 (KIQNFRVYYR) induced specific CTLs in 2 and 1 of 10 chronically HIV-1-infected individuals, respectively. Thus, the former are immunodominant epitopes whereas the latter are not. These epitopes are useful for studies of AIDS immunopathogenesis and vaccine development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cells, Cultured
  • Epitopes, T-Lymphocyte* / chemistry
  • Epitopes, T-Lymphocyte* / genetics
  • Epitopes, T-Lymphocyte* / immunology
  • Gene Products, gag / chemistry
  • Gene Products, gag / immunology*
  • Gene Products, nef / chemistry
  • Gene Products, nef / immunology
  • Gene Products, pol / chemistry
  • Gene Products, pol / immunology*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology
  • HLA-A Antigens / metabolism*
  • Humans
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • nef Gene Products, Human Immunodeficiency Virus

Substances

  • Epitopes, T-Lymphocyte
  • Gene Products, gag
  • Gene Products, nef
  • Gene Products, pol
  • HLA-A Antigens
  • HLA-A*33 antigen
  • Peptides
  • nef Gene Products, Human Immunodeficiency Virus