Existence of MHC class I-restricted alloreactive CD4+ T cells reacting with peptide transporter-deficient cells

H. Kobayashi, S. Kimura, N. Aoki, K. Sato, Esteban Celis, M. Katagiri

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

It is generally accepted that as the result of positive thymic selection, CD8-expressing T cells recognize peptide antigens presented in the context of MHC class I molecules and CD4-expressing T cells interact with peptide antigens presented by MHC class II molecules. Here we report the generation of TCRα/β+, CD3+, CD4+, CD8-, MHC class I-restricted alloreactive T-cell clones which were induced using peripheral blood mononuclear cells from healthy individuals following in vitro stimulation with transporter associated with antigen processing (TAP)-deficient cell lines T2. The CD4+ T-cell clones showed an HLA-A2.1-specific proliferative response against T2 cells which was inhibited by anti-CD3 and anti-CD4 monoclonal antibodies. These results suggest that interaction of the TCR with peptide-bound HLA class I molecules contributes to antigen-specific activation of these co-receptor-mismatched T-cell clones. Antigen recognition by alloreactive MHC class I-restricted CD4+ T cells was inhibited by removing peptides bound to HLA molecules on T2 cells suggesting that the alloreactive CD4+ T cells recognize peptides that bind in a TAP-independent manner to HLA-A2 molecules. The existence of such MHC class I-restricted CD4+ T cells which can recognize HLA-A2 molecules in the absence of TAP function may provide a basis for the development of immunotherapy against TAP-deficient tumor variants which would be tolerant to immunosurveillance by conventional MHC class I-restricted cytotoxic lymphocytes.

Original languageEnglish (US)
Pages (from-to)626-633
Number of pages8
JournalImmunogenetics
Volume53
Issue number8
DOIs
Publication statusPublished - Jan 1 2001
Externally publishedYes

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Keywords

  • Allorecognition
  • Helper T cell
  • MHC
  • Peptide
  • Transporter

ASJC Scopus subject areas

  • Immunology
  • Genetics

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