A Novel Population of Human Melanoma-Specific CD8 T Cells Recognizes Melan-A MART-1 Immunodominant Nonapeptide but Not the Corresponding Decapeptide
| Autor: | Laurent Derré, Cédric Touvrey, Olivier Michielin, Pedro Romero, Frédéric Lévy, Daniel E. Speiser, Estelle Devevre, Vincent Zoete, Mathias Ferber, Antoine Leimgruber |
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| Přispěvatelé: | Université de Lausanne (UNIL), Swiss Institute of Bioinformatics [Lausanne] (SIB), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Protein Conformation medicine.medical_treatment T cell [SDV]Life Sciences [q-bio] Immunology Population Receptors Antigen T-Cell CD8-Positive T-Lymphocytes Biology Protein Structure Secondary Epitope 03 medical and health sciences Antigens Neoplasm/immunology Binding Sites CD8-Positive T-Lymphocytes/immunology Cell Line Tumor Cloning Molecular Humans Immunodominant Epitopes/immunology MART-1 Antigen Melanoma/immunology Neoplasm Proteins/immunology Peptide Fragments/chemical synthesis Peptide Fragments/immunology Receptors Antigen T-Cell/immunology 0302 clinical medicine Antigen Antigens Neoplasm medicine Immunology and Allergy Cytotoxic T cell education Melanoma 030304 developmental biology 0303 health sciences education.field_of_study Immunodominant Epitopes T-cell receptor Immunotherapy Molecular biology Peptide Fragments Neoplasm Proteins Cytolysis medicine.anatomical_structure [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology 030215 immunology |
| Zdroj: | Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2007, 179 (11), pp.7635-7645. ⟨10.4049/jimmunol.179.11.7635⟩ Journal of Immunology, vol. 179, no. 11, pp. 7635-7645 |
| ISSN: | 0022-1767 1550-6606 |
| DOI: | 10.4049/jimmunol.179.11.7635⟩ |
| Popis: | HLA-A2-restricted cytolytic T cells specific for the immunodominant human tumor Ag Melan-AMART-1 can kill most HLA-matched melanoma cells, through recognition of two naturally occurring antigenic variants, i.e., Melan-A nonamer AAGIGILTV and decamer EAAGIGILTV peptides. Several previous studies have suggested a high degree of TCR cross-reactivity to the two peptides. In this study, we describe for the first time that some T cell clones are exclusively nonamer specific, because they are not labeled by A2/decamer-tetramers and do not recognize the decamer when presented endogenously. Functional assays with peptides gave misleading results, possibly because decamers were cleaved by exopeptidases. Interestingly, nonapeptide-specific T cell clones were rarely Vα2.1 positive (only 1 of 19 clones), in contrast to the known strong bias for Vα2.1-positive TCRs found in decamer-specific clones (59 of 69 clones). Molecular modeling revealed that nonapeptide-specific TCRs formed unfavorable interactions with the decapeptide, whereas decapeptide-specific TCRs productively created a hydrogen bond between CDR1α and glutamic acid (E) of the decapeptide. Ex vivo analysis of T cells from melanoma metastases demonstrated that both nonamer and decamer-specific T cells were enriched to substantial frequencies in vivo, and representative clones showed efficient tumor cell recognition and killing. We conclude that the two peptides should be regarded as distinct epitopes when analyzing tumor immunity and developing immunotherapy against melanoma. |
| Databáze: | OpenAIRE |
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