Cytotoxic T-lymphocyte Clones From Different Patients Display Limited T-cell-receptor Variable-region Gene Usage in Hla-a2-restricted Recognition of the Melanoma Antigen Melan-a/mart-1

Sensi, M.;Traversari, C.;Radrizzani, M.;Salvi, S.;Parmiani, G.;et.al.
(1995) National Academy of Sciences. Proceedings — Vol. 92, n° 12, p. 5674-5678 (1995)

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Authors
  • Sensi, M.
    Author
  • Traversari, C.
    Author
  • Radrizzani, M.
    Author
  • Salvi, S.
    Author
  • Boon, ThierryUCLouvain
    Author
  • Parmiani, G.
    Author
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Abstract
To determine whether T-cell-receptor (TCR) usage by T cells recognizing a defined human tumor antigen in the context of the same HLA molecule is conserved, we analyzed the TCR diversity of autologous HLA-A2-restricted cytotoxic T-lymphocyte (CTL) clones derived from five patients with metastatic melanoma and specific for the common melanoma antigen Melan-A/MART-1. These clones were first identified among HLA-A2-restricted anti-melanoma CTL clones by their ability to specifically release tumor necrosis factor in response to HLA-A2.1(+) COS-7 cells expressing this tumor antigen, A PCR with variable (V)-region gene subfamily-specific primers was performed on cDNA from each clone followed by DNA sequencing, TCRAV2S1 was the predominant alpha-chain V region, being transcribed in 6 out of 9 Melan-A/MART-1-specific CTL clones obtained from the five patients. beta-chain V-region usage was also restricted, with either TCRBV14 or TCRBV7 expressed by all but one clone. In addition, a conserved TCRAV2S1/TCRBV14 combination was expressed in four CTL clones from three patients, None of these V-region genes was found in a group of four HLA-A2-restricted CTL clones recognizing different antigens (e.g., tyrosinase) on the autologous tumor, TCR joining regions were heterogeneous, although conserved structural features were observed in the complementarity-determining region 3 sequences, These results indicate that a selective repertoire of TCR genes is used in anti-melanoma responses when the response is narrowed to major histocompatibility complex-restricted antigen-specific interactions.
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Sensi, M., Traversari, C., Radrizzani, M., Salvi, S., Maccalli, C., Mortarini, R., Rivoltini, L., Farina, C., Nicolini, G., Wolfel, T., Brichard, V., Boon, T., Bordignon, C., Anichini, A., & Parmiani, G. (1995). Cytotoxic T-lymphocyte Clones From Different Patients Display Limited T-cell-receptor Variable-region Gene Usage in Hla-a2-restricted Recognition of the Melanoma Antigen Melan-a/mart-1. National Academy of Sciences. Proceedings, 92(12), 5674-5678. https://doi.org/10.1073/pnas.92.12.5674 (Original work published 1995)