MHC class I-restricted recognition of a melanoma antigen by a human CD4+ tumor infiltrating lymphocyte

Michael I. Nishimura, Dody Avichezer, Mary C. Custer, Catherine S. Lee, Christine Chen, Maria R. Parkhurst, Rochelle A. Diamond, Paul F. Robbins, Douglas J. Schwartzentruber, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

It is generally considered that MHC Class I-restricted antigens are recognized by CD8+ T cells, whereas MHC Class II-restricted antigens are recognized by CD4+ T cells. In the present study, we report an MHC class I- restricted CD4+ T cell isolated from the tumor infiltrating lymphocytes (TILs) of a patient with metastatic melanoma. TIL 1383 I recognized HLA-A2+ melanoma cell lines but not autologous transformed B cells or fibroblasts. The antigen recognized by TIL 1383 I was tyrosinase, and the epitope was the 368-376 peptide. Antibody blocking assays confirmed that TIL 1383 I was MHC class I restricted, and the CD4 and CD8 coreceptors did not contribute significantly to antigen recognition. TIL 1383 I was weakly cytolytic and secreted cytokines in a pattern consistent with it being a T(h1) cell. The avidity of TIL 1383 I for peptide pulsed targets is 10-100-fold lower than most melanoma-reactive CD8+ T cell clones. These CD4+ T cells may represent a relatively rare population of T cells that express a T-cell receptor capable of cross-reacting with an MHC class I/peptide complex with sufficient affinity to allow triggering in the absence of the CD4 coreceptor.

Original languageEnglish (US)
Pages (from-to)6230-6238
Number of pages9
JournalCancer Research
Volume59
Issue number24
StatePublished - Dec 15 1999

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nishimura, M. I., Avichezer, D., Custer, M. C., Lee, C. S., Chen, C., Parkhurst, M. R., Diamond, R. A., Robbins, P. F., Schwartzentruber, D. J., & Rosenberg, S. A. (1999). MHC class I-restricted recognition of a melanoma antigen by a human CD4+ tumor infiltrating lymphocyte. Cancer Research, 59(24), 6230-6238.