Melanoma-specific CD4+ T lymphocytes recognize human melanoma antigens processed and presented by Epstein-Barr virus-transformed B cells

S. L. Topalian, L. Rivoltini, M. Mancini, J. Ng, R. J. Hartzman, S. A. Rosenberg

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Abstract

While much emphasis has been placed on the role of MHC class I-restricted CD8+ T cells in the recognition of tumor-specific antigens (Ag), evidence has accumulated that CD4+ T cells also play a critical role in the anti-tumor immune response. However, little information exists on the nature of MHC class II-restricted human tumor Ag. In an attempt to develop in vitro systems to characterize such Ag, we examined the ability of Epstein-Barr virus(EBV)-transformed B cells to present melanoma-associated Ag to melanoma-specific CD4+ cells. CD4+ T cells cultured from lymphocytes infiltrating a s.c. melanoma metastasis secreted TNF-α and GM-CSF specifically in response to autologous cultured melanoma cells expressing MHC class II molecules. These CD4+ cells also recognized MHC class II-compatible EBV-B cells pulsed with extracts of autologous melanoma cells, but failed to recognize EBV-B cells pulsed with autologous non-transformed cells or a variety of allogeneic tumors or normal cells. B cells pre-fixed with paraformaldehyde were incapable of Ag presentation, suggesting that intracellular processing events were occurring. Antibody-blocking studies defined HLA-DR as the dominant if not exclusive restriction locus in this T-B interaction, and HLA-DR genotyping revealed DRB I *0404 to be the probable restriction element. In a second patient, a CD4+ T-cell clone cultured from a melanoma lesion recognized autologous tumor Ag presented by autologous EBV-B; no cross-reactivity was observed with the other tumor system investigated, nor with autologous CD4+ T cells specific for tetanus toxoid. These findings demonstrate that tumor Ag can be processed and presented by EBV-transformed B cells to MHC class II-restricted tumor-specific CD4+ T cells. They also provide a model system for direct identification of these tumor-derived antigens.

Original languageEnglish
Pages (from-to)69-79
Number of pages11
JournalInternational Journal of Cancer
Volume58
Issue number1
DOIs
Publication statusPublished - 1994

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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