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

• Published in: Cancer research (Chicago, Ill.) Vol. 59; no. 24; pp. 6230 - 6238
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-12-1999
• Subjects: Antigens, Neoplasm - immunology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Cytokines - immunology; Histocompatibility Antigens Class I - immunology; HLA-A2 Antigen - immunology; Host-tumor relations. Immunology. Biological markers; Humans; Lymphocytes, Tumor-Infiltrating - immunology; Medical sciences; Melanoma - blood; Melanoma - immunology; Tumor Cells, Cultured; Tumors; Human; Immune response; Antigenic determinant; Enzyme; Major histocompatibility system; Lyases; Cellular immunity; Tumor infiltrating lymphocyte; Malignant tumor; In vitro; Carbon-carbon lyases; T-Lymphocyte; Malignant melanoma; Advanced stage; Tyrosine phenol-lyase; Class I histocompatibility antigen; Tumor cell
• ISSN: 0008-5472; 1538-7445

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.