MHC class I-restricted recognition of a melanoma antigen by a human CD4+ tumor infiltrating lymphocyte
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.
Cancer Research 59(24): 6230-6238
1999
ISSN/ISBN: 0008-5472 PMID: 10626817 Document Number: 507284
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 Th1 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.