T cell-receptor V gene use by CD4+ melanoma-reactive clonal and oligoclonal T-cell lines

Michael I. Nishimura, Mary C. Custer, Susan L. Schwarz, Linda L. Parker, Arnold Mixon, Timothy M. Clay, John R. Yannelli, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

Tumor-reactive CD4+ T cells can be isolated and expanded from the peripheral blood and tumor lesions of patients with melanoma. In contrast to CD8+ T cells, little is known about the antigens recognized by these CD4+ T cells. As a consequence, little is known about the diversity of the T-cell receptor (TcR) use by melanoma-reactive CD4+ T cells. To address these questions, a panel of clonal or highly oligoclonal CD4+ T-cell lines was established from a patient with metastatic melanoma. A CD4+ tumor-infiltrating lymphocyte (TIL) line was established that was highly oligoclonal and recognized only autologous melanoma cells but not allogeneic melanomas, suggesting the expression of a mutated or uniquely expressed antigen by this melanoma. The antigen recognized by the CD4+ TILs could be presented by intact melanoma cells or by autologous Epstein-Barr virus (EBV) B cells pulsed with melanoma cell lysates. A panel of CD4+ clonal and highly oligoclonal T-cell lines was isolated from peripheral blood mononuclear cells (PBMC) from this patient; these were also reactive with autologous melanoma cells or tumor extracts pulsed on autologous EBV B cells. Despite their reactivity with the autologous melanoma, we found no evidence of restricted TcR V gene use, because all six T-cell lines recognized antigen via different TcR α/β rearrangements. Furthermore, there were no conserved amino acids in the CDR3 regions of these TcRs, indicating that multiple TcR clono-types could mediate recognition of a single unique major histocompatibility (MHC) complex class II restricted melanoma antigen or that multiple MHC class II restricted melanoma antigens are expressed by the melanoma.

Original languageEnglish (US)
Pages (from-to)352-362
Number of pages11
JournalJournal of Immunotherapy
Volume21
Issue number5
DOIs
StatePublished - Jan 1 1998

Keywords

  • CD4 T cells
  • Melanoma antigen
  • T-cell receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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    Nishimura, M. I., Custer, M. C., Schwarz, S. L., Parker, L. L., Mixon, A., Clay, T. M., Yannelli, J. R., & Rosenberg, S. A. (1998). T cell-receptor V gene use by CD4+ melanoma-reactive clonal and oligoclonal T-cell lines. Journal of Immunotherapy, 21(5), 352-362. https://doi.org/10.1097/00002371-199809000-00003