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 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.
Additional Information
© 1999 American Association for Cancer Research. Received May 7, 1999; Accepted October 19, 1999. We thank Drs. John R. Wunderlich, Suzanne L. Topalian, Timothy Clay, and Alfred Singer for thoughtful suggestions and critical reading of the manuscript. We also thank Pat Koen and Arnold Mixon for valuable assistance with flow cytometry. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.Additional details
- Eprint ID
- 95460
- Resolver ID
- CaltechAUTHORS:20190514-073207007
- Created
-
2019-05-14Created from EPrint's datestamp field
- Updated
-
2019-10-03Created from EPrint's last_modified field