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

It is generally considered that MNC class I-restricted antigens are recogni zed by CD8(+) T cells, whereas MBC class II-restricted antigens are recogni zed by CD4(+) T cells, In the present study, we report an MHC class I-restr icted CD4(+) T cell isolated from the tumor infiltrating lymphocytes (TILs) of a patient with metastatic melanoma, TIL 1383 I recognized HLA-A2(+) mel anoma cell lines but not autologous transformed B cells or fibroblasts, The antigen recognized by TIL 1383 I was tyrosinase, and the epitope was the 3 68-376 peptide. Antibody blocking assays confirmed that TIL 1383 I was MHC class I restricted, and the CD4 and CD8 coreceptors did not contribute sign ificantly to antigen recognition, TIL 1383 I was weakly cytolytic and secre ted cytokines in a pattern consistent with it being a T-h1 cell, The avidit y of TIL 1383 I for peptide pulsed targets is 10-100-fold lower than most m elanoma-reactive CD8(+) T cell clones. These CD4(+) T cells may represent a relatively rare population of T cells that express a T-cell receptor capab le of cross-reacting with an MHC class I/peptide complex with sufficient af finity to allow triggering in the absence of the CD4 coreceptor.