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 clonotypes 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
StatePublished - 1998
Externally publishedYes

Fingerprint

T-Cell Receptor Genes
Melanoma
T-Lymphocytes
Cell Line
Melanoma-Specific Antigens
T-Cell Antigen Receptor
CD4 Antigens
Human Herpesvirus 4
B-Lymphocytes
Tumor-Infiltrating Lymphocytes
Neoplasms
Histocompatibility
Major Histocompatibility Complex
Blood Cells

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Nishimura, M. I., Custer, M. C., Schwarz, S. L., Parker, L. L., Mixon, A., Clay, T. M., ... 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.

T cell-receptor V gene use by CD4+ melanoma-reactive clonal and oligoclonal T-cell lines. / Nishimura, Michael I.; Custer, Mary C.; Schwarz, Susan L.; Parker, Linda L.; Mixon, Arnold; Clay, Timothy M.; Yannelli, John R.; Rosenberg, Steven A.

In: Journal of Immunotherapy, Vol. 21, No. 5, 1998, p. 352-362.

Research output: Contribution to journalArticle

Nishimura, MI, Custer, MC, Schwarz, SL, Parker, LL, Mixon, A, Clay, TM, Yannelli, JR & Rosenberg, SA 1998, 'T cell-receptor V gene use by CD4+ melanoma-reactive clonal and oligoclonal T-cell lines', Journal of Immunotherapy, vol. 21, no. 5, pp. 352-362.
Nishimura MI, Custer MC, Schwarz SL, Parker LL, Mixon A, Clay TM et al. T cell-receptor V gene use by CD4+ melanoma-reactive clonal and oligoclonal T-cell lines. Journal of Immunotherapy. 1998;21(5):352-362.
Nishimura, Michael I. ; Custer, Mary C. ; Schwarz, Susan L. ; Parker, Linda L. ; Mixon, Arnold ; Clay, Timothy M. ; Yannelli, John R. ; Rosenberg, Steven A. / T cell-receptor V gene use by CD4+ melanoma-reactive clonal and oligoclonal T-cell lines. In: Journal of Immunotherapy. 1998 ; Vol. 21, No. 5. pp. 352-362.
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