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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MART-1 Antigen
Melanoma-Specific Antigens
HLA-A2 Antigen
Cytotoxic T-Lymphocytes
T-Cell Antigen Receptor
Clone Cells
Genes
Melanoma
Neoplasm Antigens
Complementarity Determining Regions
T-Cell Receptor Genes
Antigens
Monophenol Monooxygenase
COS Cells
Major Histocompatibility Complex
DNA Sequence Analysis
Complementary DNA
Tumor Necrosis Factor-alpha
T-Lymphocytes
Polymerase Chain Reaction

ASJC Scopus subject areas

  • General

Cite this

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.; Maccalli, Cristina; Mortarini, R.; Rivoltini, L.; Farina, C.; Nicolini, G.; Wolfel, T.; Brichard, V.; Boon, T.; Bordignon, C.; Anichini, A.; Parmiani, G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 12, 1995, p. 5674-5678.

Research output: Contribution to journalArticle

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, vol. 92, no. 12, pp. 5674-5678. https://doi.org/10.1073/pnas.92.12.5674
Sensi, M. ; Traversari, C. ; Radrizzani, M. ; Salvi, S. ; Maccalli, Cristina ; Mortarini, R. ; Rivoltini, L. ; Farina, C. ; Nicolini, G. ; Wolfel, T. ; Brichard, V. ; Boon, T. ; Bordignon, C. ; Anichini, A. ; Parmiani, G. / 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. In: Proceedings of the National Academy of Sciences of the United States of America. 1995 ; Vol. 92, No. 12. pp. 5674-5678.
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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.",
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T1 - 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

AU - Sensi, M.

AU - Traversari, C.

AU - Radrizzani, M.

AU - Salvi, S.

AU - Maccalli, Cristina

AU - Mortarini, R.

AU - Rivoltini, L.

AU - Farina, C.

AU - Nicolini, G.

AU - Wolfel, T.

AU - Brichard, V.

AU - Boon, T.

AU - Bordignon, C.

AU - Anichini, A.

AU - Parmiani, G.

PY - 1995

Y1 - 1995

N2 - 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.

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