A novel population of human melanoma-specific CD8 T cells recognizes Melan-AMART-1 immunodominant nonapeptide but not the corresponding decapeptide.

Détails

Ressource 1Télécharger: BIB_C81EFE777B85.P001.pdf (731.55 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_C81EFE777B85
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A novel population of human melanoma-specific CD8 T cells recognizes Melan-AMART-1 immunodominant nonapeptide but not the corresponding decapeptide.
Périodique
Journal of Immunology
Auteur(s)
Derré L., Ferber M., Touvrey C., Devevre E., Zoete V., Leimgruber A., Romero P., Michielin O., Lévy F., Speiser D.E.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2007
Volume
179
Numéro
11
Pages
7635-7645
Langue
anglais
Résumé
HLA-A2-restricted cytolytic T cells specific for the immunodominant human tumor Ag Melan-A(MART-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 Valpha2.1 positive (only 1 of 19 clones), in contrast to the known strong bias for Valpha2.1-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 CDR1alpha 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.
Mots-clé
Antigens, Neoplasm/immunology, Binding Sites, CD8-Positive T-Lymphocytes/immunology, Cell Line, Tumor, Cloning, Molecular, Humans, Immunodominant Epitopes/immunology, MART-1 Antigen, Melanoma/immunology, Models, Molecular, Neoplasm Proteins/immunology, Peptide Fragments/chemical synthesis, Peptide Fragments/immunology, Protein Conformation, Protein Structure, Secondary, Receptors, Antigen, T-Cell/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/09/2011 21:04
Dernière modification de la notice
09/05/2019 1:08
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