Article: article from journal or magazin.
Tetramer-guided analysis of TCR beta-chain usage reveals a large repertoire of melan-A-specific CD8+ T cells in melanoma patients.
Journal of Immunology
Publication types: Journal Article. - Old month value: Jul 1
The assessment of the TCR repertoire expressed by tumor-specific CD8+ T lymphocytes has been hampered to date by the difficulty of targeting the analysis to lymphocytes directed against a single epitope. In the present study we have used fluorescent A2/Melan-A tetramers in conjunction with anti-CD8 and anti-TCR beta-chain variable (BV) mAbs to analyze by flow cytometry the BV segment usage by Melan-A-specific CD8+ T cells in tumor-infiltrated lymph nodes (TILN) and tumor-infiltrating lymphocytes (TIL) from A2 melanoma patients. Analysis of TILN populations revealed small proportions of A2/Melan-A tetramer+ cells expressing many different BV together with over-representation of A2/Melan-A tetramer+ cells expressing certain BVs. The BV usage by A2/Melan-A tetramer+ lymphocytes in TIL was more restricted than that in TILN. Moreover, the predominant BV segments were quite distinct in populations derived from different patients. A2/Melan-A tetramer+ cells expressing the dominant BVs found in TILN could also be found in the corresponding peptide-stimulated autologous PBMC, although A2/Melan-A tetramer+ lymphocytes expressing additional BVs were also identified. Together, these results suggest that a large and diverse repertoire of Melan-A-specific T cells using different BV TCR segments is available in A2 melanoma patients.
Adult, Aged, Antigens, Neoplasm/metabolism, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Epitopes, T-Lymphocyte/metabolism, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Genes, T-Cell Receptor beta, Humans, Leukocytes, Mononuclear/immunology, Leukocytes, Mononuclear/metabolism, Lymphocyte Activation/immunology, Lymphocyte Count, Lymphocytes, Tumor-Infiltrating/immunology, Lymphocytes, Tumor-Infiltrating/metabolism, Melanoma/immunology, Melanoma/metabolism, Middle Aged, Neoplasm Proteins/biosynthesis, Neoplasm Proteins/immunology, Peptide Fragments/immunology, Tumor Cells, Cultured
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