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

M. Sensi, C. Traversari, M. Radrizzani, S. Salvi, Cristina Maccalli, R. Mortarini, L. Rivoltini, C. Farina, G. Nicolini, T. Wolfel, V. Brichard, T. Boon, C. Bordignon, A. Anichini, G. Parmiani

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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 α-chain V region, being transcribed in 6 out of 9 Melan-A/MART-1-specific CTL clones obtained from the five patients. β-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.

Original languageEnglish
Pages (from-to)5674-5678
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number12
DOIs
Publication statusPublished - 1995
Externally publishedYes

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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. Proceedings of the National Academy of Sciences of the United States of America, 92(12), 5674-5678. https://doi.org/10.1073/pnas.92.12.5674