Characterization of the functional specificity of a cloned T-cell receptor heterodimer recognizing the MART-1 melanoma antigen

D. J. Cole, D. P. Weil, J. Shilyansky, M. Custer, Yutaka Kawakami, S. A. Rosenberg, M. I. Nishimura

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

T cells can play a central role in the immune response to cancer, with tumor-specific T-lymphocyte reactivity provided by the T-cell receptor (TCR) α and β chain heterodimer. This study is the first report of the definitive identification and characterization of a functional tumor-associated, antigen-specific TCR by reconstitution in an alternate cell line. Jurkat T cells were transfected with the cDNAs encoding the full-length α and β T- cell receptor chains from the HLA-A2 restricted, melanoma-reactive T-cell clone, clone 5. Expression of the transfected TCR was evaluated by immunofluorescence after down-modulation of the endogenous receptor with Jurkat T-cell receptor β chain-specific mAb. Jurkat clone 5 TCR+ cells recognized MART-1 peptides presented by T2 cells in a pattern and sensitivity equivalent to native MART-1-reactive T-cells. Recognition of HLA-A2+ melanoma cell lines by the Jurkat clone 5 TCR+ cells, however, did not occur without the addition of exogenous MART-1 peptide. The cloning and expression of functional TCR genes which are capable of specifically recognizing MART-1 antigen provides reagents which could be used for the study of the mechanisms of T-cell/tumor antigen interactions and creates immortalized reagents which can facilitate studies requiring detection of the MART-1 antigen. The tumor reactivity provided by these genes could also have application in novel immunotherapeutic strategies for treating patients with melanoma, including redirection of tumor-infiltrating lymphocyte specificity and bone marrow stem cell therapy.

Original languageEnglish
Pages (from-to)748-752
Number of pages5
JournalCancer Research
Volume55
Issue number4
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

MART-1 Antigen
Melanoma-Specific Antigens
T-Cell Antigen Receptor
T-Lymphocytes
Clone Cells
HLA-A2 Antigen
Melanoma
Jurkat Cells
Neoplasm Antigens
Tumor-Infiltrating Lymphocytes
T-Cell Receptor Genes
Cell Line
Neoplasms
Peptides
Cell- and Tissue-Based Therapy
Bone Marrow Cells
Fluorescent Antibody Technique
Organism Cloning
Stem Cells
Complementary DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cole, D. J., Weil, D. P., Shilyansky, J., Custer, M., Kawakami, Y., Rosenberg, S. A., & Nishimura, M. I. (1995). Characterization of the functional specificity of a cloned T-cell receptor heterodimer recognizing the MART-1 melanoma antigen. Cancer Research, 55(4), 748-752.

Characterization of the functional specificity of a cloned T-cell receptor heterodimer recognizing the MART-1 melanoma antigen. / Cole, D. J.; Weil, D. P.; Shilyansky, J.; Custer, M.; Kawakami, Yutaka; Rosenberg, S. A.; Nishimura, M. I.

In: Cancer Research, Vol. 55, No. 4, 1995, p. 748-752.

Research output: Contribution to journalArticle

Cole, DJ, Weil, DP, Shilyansky, J, Custer, M, Kawakami, Y, Rosenberg, SA & Nishimura, MI 1995, 'Characterization of the functional specificity of a cloned T-cell receptor heterodimer recognizing the MART-1 melanoma antigen', Cancer Research, vol. 55, no. 4, pp. 748-752.
Cole DJ, Weil DP, Shilyansky J, Custer M, Kawakami Y, Rosenberg SA et al. Characterization of the functional specificity of a cloned T-cell receptor heterodimer recognizing the MART-1 melanoma antigen. Cancer Research. 1995;55(4):748-752.
Cole, D. J. ; Weil, D. P. ; Shilyansky, J. ; Custer, M. ; Kawakami, Yutaka ; Rosenberg, S. A. ; Nishimura, M. I. / Characterization of the functional specificity of a cloned T-cell receptor heterodimer recognizing the MART-1 melanoma antigen. In: Cancer Research. 1995 ; Vol. 55, No. 4. pp. 748-752.
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