title: MHC class I-restricted recognition of a melanoma antigen by a human CD4+ tumor infiltrating lymphocyte.
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 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.
authors.affiliation: Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. nishimur@helix.nih.gov
authors.forename: M I
authors.initials: MI
authors.lastname: Nishimura
authors.forename: D
authors.initials: D
authors.lastname: Avichezer
authors.forename: M C
authors.initials: MC
authors.lastname: Custer
authors.forename: C S
authors.initials: CS
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: M R
authors.initials: MR
authors.lastname: Parkhurst
authors.forename: R A
authors.initials: RA
authors.lastname: Diamond
authors.forename: P F
authors.initials: PF
authors.lastname: Robbins
authors.forename: D J
authors.initials: DJ
authors.lastname: Schwartzentruber
authors.forename: S A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000097:blood / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I