Impact of orthologous melan-A peptide immunizations on the anti-self melan-A/HLA-A2 T cell cross-reactivity.

Détails

ID Serval
serval:BIB_FF36BB0A3BB5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Impact of orthologous melan-A peptide immunizations on the anti-self melan-A/HLA-A2 T cell cross-reactivity.
Périodique
Journal of Immunology
Auteur(s)
Colombetti S., Fagerberg T., Baumgärtner P., Chapatte L., Speiser D.E., Rufer N., Michielin O., Lévy F.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2006
Peer-reviewed
Oui
Volume
176
Numéro
11
Pages
6560-6567
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
In HLA-A2 individuals, the CD8 T cell response against the differentiation Ag Melan-A is mainly directed toward the peptide Melan-A26-35. The murine Melan-A24-33 sequence encodes a peptide that is identical with the human Melan-A26-35 decamer, except for a Thr-to-Ile substitution at the penultimate position. Here, we show that the murine Melan-A24-33 is naturally processed and presented by HLA-A2 molecules. Based on these findings, we compared the CD8 T cell response to human and murine Melan-A peptide by immunizing HLA-A2 transgenic mice. Even though the magnitude of the CTL response elicited by the murine Melan-A peptide was lower than the one elicited by the human Melan-A peptide, both populations of CTL recognized the corresponding immunizing peptide with the same functional avidity. Interestingly, CTL specific for the murine Melan-A peptide were completely cross-reactive against the orthologous human peptide, whereas anti-human Melan-A CTL recognized the murine Melan-A peptide with lower avidity. Structurally, this discrepancy could be explained by the fact that Ile32 of murine Melan-A24-33 created a larger TCR contact area than Thr34 of human Melan-A26-35. These data indicate that, even if immunizations with orthologous peptides can induce strong specific T cell responses, the quality of this response against syngeneic targets might be suboptimal due to the structure of the peptide-TCR contact surface.
Mots-clé
Amino Acid Sequence, Animals, Antigens, Neoplasm, Autoantigens/immunology, Autoantigens/metabolism, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Cancer Vaccines/administration & dosage, Cancer Vaccines/immunology, Cell Line, Clone Cells, Cross-Priming/genetics, Epitopes, T-Lymphocyte/chemistry, Epitopes, T-Lymphocyte/immunology, H-2 Antigens/genetics, H-2 Antigens/immunology, HLA-A2 Antigen/administration & dosage, HLA-A2 Antigen/genetics, Humans, MART-1 Antigen, Melanoma, Experimental, Mice, Mice, Transgenic, Molecular Sequence Data, Neoplasm Proteins/administration & dosage, Neoplasm Proteins/immunology, Peptides/administration & dosage, Peptides/immunology, T-Lymphocytes, Cytotoxic/immunology, T-Lymphocytes, Cytotoxic/metabolism
Pubmed
Web of science
Création de la notice
28/01/2008 12:17
Dernière modification de la notice
20/08/2019 17:29
Données d'usage