Human CD4+ T cells specifically recognize a shared melanoma-associated antigen encoded by the tyrosinase gene

Suzanne L. Topalian, Licia Rivoltini, Marie Mancini, Nancy R. Markus, Paul F. Robbins, Yutaka Kawakami, Steven A. Rosenberg

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260 Citations (Scopus)

Abstract

Although commonly expressed human melanoma-associated antigens recognized by CD8+ cytolytic T cells have been described, little is known about CD4+ T-cell recognition of melanoma-associated antigens. Epstein-Barr virus- transformed B cells were used to present antigens derived from whole cell lysates of autologous and allogeneic melanomas for recognition by melanoma- specific CD4+ T-cell lines and clones cultured from tumor-infiltrating lymphocytes. HLA-DR-restricted antigens were detected in the lysates on the basis of specific release of cytokines from the responding T cells. Antigen sharing was demonstrated in the majority of melanomas tested, as well as in cultured normal melanocytes, but not in other normal tissues or nonmelanoma tumors. T-cell clones manifested a single recognition pattern, suggesting the presence of an immunodominant epitope. This epitope was identified as a product of the tyrosinase gene, which has also been shown to encode class I- restricted epitopes recognized by CD8+ T cells from melanoma patients. Identification of commonly expressed tumor-associated protein molecules containing epitopes presented by both class I and class II major histocompatibility molecules may provide optimal reagents for cancer immunization strategies.

Original languageEnglish
Pages (from-to)9461-9465
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number20
DOIs
Publication statusPublished - 1994 Sep 27

ASJC Scopus subject areas

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