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

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Version: Final published version
Serval ID
serval:BIB_C81EFE777B85
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A novel population of human melanoma-specific CD8 T cells recognizes Melan-AMART-1 immunodominant nonapeptide but not the corresponding decapeptide.
Journal
Journal of Immunology
Author(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
Publication state
Published
Issued date
2007
Volume
179
Number
11
Pages
7635-7645
Language
english
Abstract
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.
Keywords
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
Yes
Create date
03/09/2011 21:04
Last modification date
20/08/2019 16:43
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