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  • Title: Human CD4+ T cells specifically recognize a shared melanoma-associated antigen encoded by the tyrosinase gene.
    Author: Topalian SL, Rivoltini L, Mancini M, Markus NR, Robbins PF, Kawakami Y, Rosenberg SA.
    Journal: Proc Natl Acad Sci U S A; 1994 Sep 27; 91(20):9461-5. PubMed ID: 7937789.
    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.
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