Identification of multiple HIV-1 cytotoxic T-cell epitopes presented by human leukocyte antigen B35 molecules.
OBJECTIVE
To identify HIV-1 cytotoxic T lymphocyte (CTL) epitopes presented by human leukocyte antigen (HLA)-B35 molecules that are associated with the accelerated progression of AIDS using a reverse immunogenetic approach.


METHODS
8-mer to 11-mer sequences carrying two anchor residues at position 2 and the carboxy-terminus were selected from HIV-1SF2 strain. Sixty-four peptides matched to these sequences were synthesized and tested by a peptide binding assay using RMA-S-B*3501 cells. Peripheral blood lymphocytes (PBL) from two HIV-1-infected donors carrying HLA-B35 were stimulated once-weekly with each HLA-B*3501 binding peptide. The CTL activity of the cultured cells for the HLA-B35-positive target cells loaded with the corresponding peptides was examined after the second and fourth stimulation. Furthermore, the CTL activity of the cultured cells possessing HLA-B*3501-restricted HIV-1 peptide-specific CTL activity were examined for the HLA-B*3501-positive target cells infected with the recombinant vaccinia virus containing corresponding HIV-1 gene.


RESULTS
HIV-1 peptide-specific HLA-B*3501-restricted CTL was induced in PBL of HIV-1 infected donors by in vitro stimulation with 11 out of 27 HLA-B*3501-binding HIV-1 peptides. The specific CTL induced with 10 peptides killed the cells infected with recombinant vaccinia virus expressing the corresponding HIV-1 proteins. Out of these HIV-1 peptide epitopes, two epitopes were also presented by HLA-B51 molecules.


CONCLUSIONS
In addition to the four HLA-B35-restricted HIV-1 CTL epitopes that have been previously reported, nine HLA-B35-restricted HIV-1 CTL epitopes were identified in the present study. These multiple epitopes will be useful in studies for immunopathogenesis of AIDS.
Shiga
H
H
Institute of Medical Science, University of Tokyo, Japan.
Shioda
T
T
Tomiyama
H
H
Takamiya
Y
Y
Oka
S
S
Kimura
S
S
Yamaguchi
Y
Y
Gojoubori
T
T
Rammensee
H G
HG
Miwa
K
K
Takiguchi
M
M
D017951:Antigen Presentation; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology; D015797:HLA-B35 Antigen / Q000276:immunology*; D059949:HLA-B51 Antigen; D006801:Humans; D009154:Mutation; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
D000939:Epitopes; D015235:HLA-B Antigens; D015797:HLA-B35 Antigen; D059949:HLA-B51 Antigen; D009842:Oligopeptides; D011994:Recombinant Proteins