Identification of multiple HIV-1 cytotoxic T-cell epitopes presented by human leukocyte antigen B35 molecules

Hajime Shiga, Tatsuo Shioda, Hiroko Tomiyama, Yuji Takamiya, Shinichi Oka, Satoshi Kimura, Yumi Yamaguchi, Takashi Gojoubori, Hans Georg Rammensee, Kiyoshi Miwa, Masafumi Takiguchi

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

Objectives: 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-1(SF2) 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1075-1083
Number of pages9
JournalAIDS
Volume10
Issue number10
Publication statusPublished - 1996 Sep 9
Externally publishedYes

Keywords

  • Cytotoxic T lymphocyte epitope
  • HIV-1
  • HLA-B35
  • Reverse immunogenetics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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