Identification and characterization of HLA-A*3303-restricted, HIV type 1 Pol- and Gag-derived cytotoxic T cell epitopes.
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.
Hossain
M Sohrab
MS
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Tomiyama
Hiroko
H
Inagawa
Takafumi
T
Ida
Setsuko
S
Oka
Shinichi
S
Takiguchi
Masafumi
M
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000737:chemistry / Q000276:immunology*; D015693:Gene Products, nef / Q000737:chemistry / Q000276:immunology; D015684:Gene Products, pol / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D015234:HLA-A Antigens / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015693:Gene Products, nef; D015684:Gene Products, pol; D015234:HLA-A Antigens; C082945:HLA-A*33 antigen; D010455:Peptides; D054311:nef Gene Products, Human Immunodeficiency Virus