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Immunogenetics

, Volume 53, Issue 8, pp 626–633 | Cite as

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

  • Hiroya Kobayashi
  • Shoji Kimura
  • Naoko Aoki
  • Keisuke Sato
  • Esteban Celis
  • Makoto Katagiri
Original Paper

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.

Helper T cell MHC Transporter Allorecognition Peptide 

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Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Hiroya Kobayashi
    • 1
  • Shoji Kimura
    • 1
  • Naoko Aoki
    • 1
  • Keisuke Sato
    • 1
  • Esteban Celis
    • 2
  • Makoto Katagiri
    • 1
  1. 1.Department of Pathology, Asahikawa Medical College, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan
  2. 2.Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA

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