Distinct sets of alphabeta TCRs confer similar recognition of tumor antigen NY-ESO-1157-165 by interacting with its central Met/Trp residues
| Autor: | Petra Baumgaertner, Laurent Derré, Pedro Romero, Nathalie Rufer, Marc Bruyninx, Daphné Schmid, Daniel E. Speiser, Mathias Ferber, Vincent Zoete, Antoine Leimgruber, Olivier Michielin |
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| Rok vydání: | 2008 |
| Předmět: |
Threonine
Skin Neoplasms Transcription Genetic T cell Receptors Antigen T-Cell alpha-beta Amino Acid Motifs Molecular Sequence Data chemical and pharmacologic phenomena Biology CD8-Positive T-Lymphocytes Conserved sequence Amino Acid Sequence CD8-Positive T-Lymphocytes/immunology Clone Cells Conserved Sequence Humans Melanoma/immunology Methionine/chemistry Neoplasm Proteins/immunology Peptide Fragments/immunology Receptors Antigen T-Cell alpha-beta/chemistry Receptors Antigen T-Cell alpha-beta/classification Skin Neoplasms/immunology Threonine/chemistry Methionine Antigen medicine Cytotoxic T cell Peptide sequence Melanoma Multidisciplinary T-cell receptor Biological Sciences Molecular biology Tumor antigen Peptide Fragments Neoplasm Proteins medicine.anatomical_structure CD8 |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 39, pp. 15010-15015 |
| ISSN: | 1091-6490 |
| Popis: | Naturally acquired immune responses against human cancers often include CD8+T cells specific for the cancer testis antigen NY-ESO-1. Here, we studied T cell receptor (TCR) primary structure and function of 605 HLA-A*0201/NY-ESO-1157–165-specific CD8 T cell clones derived from five melanoma patients. We show that an important proportion of tumor-reactive T cells preferentially use TCR AV3S1/BV8S2 chains, with remarkably conserved CDR3 amino acid motifs and lengths in both chains. All remaining T cell clones belong to two additional sets expressing BV1 or BV13 TCRs, associated with α-chains with highly diverse VJ usage, CDR3 amino acid sequence, and length. Yet, all T cell clonotypes recognize tumor antigen with similar functional avidity. Two residues, Met-160 and Trp-161, located in the middle region of the NY-ESO-1157–165peptide, are critical for recognition by most of the T cell clonotypes. Collectively, our data show that a large number of αβ TCRs, belonging to three distinct sets (AVx/BV1, AV3/BV8, AVx/BV13) bind pMHC with equal antigen sensitivity and recognize the same peptide motif. Finally, this in-depth study of recognition of a self-antigen suggests that in part similar biophysical mechanisms shape TCR repertoires toward foreign and self-antigens. |
| Databáze: | OpenAIRE |
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