Amino acid identity and/or position determines the proteasomal cleavage of the HLA-A*0201-restricted peptide tumor antigen MAGE-3271-279.

Détails

ID Serval
serval:BIB_15032
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Amino acid identity and/or position determines the proteasomal cleavage of the HLA-A*0201-restricted peptide tumor antigen MAGE-3271-279.
Périodique
Journal of Biological Chemistry
Auteur(s)
Miconnet I., Servis C., Cerottini J.C., Romero P., Lévy F.
ISSN
0021-9258[print], 0021-9258[linking]
Statut éditorial
Publié
Date de publication
2000
Volume
275
Numéro
35
Pages
26892-26897
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The proteasome plays a crucial role in the proteolytic processing of antigens presented to T cells in the context of major histocompatibility complex class I molecules. However, the rules governing the specificity of cleavage sites are still largely unknown. We have previously shown that a cytolytic T lymphocyte-defined antigenic peptide derived from the MAGE-3 tumor-associated antigen (MAGE-3(271-279), FLWGPRALV in one-letter code) is not presented at the surface of melanoma cell lines expressing the MAGE-3 protein. By using purified proteasome and MAGE-3(271-279) peptides extended at the C terminus by 6 amino acids, we identified predominant cleavages after residues 278 and 280 but no detectable cleavage after residue Val(279), the C terminus of the antigenic peptide. In the present study, we have investigated the influence of Pro(275), Leu(278), and Glu(280) on the proteasomal digestion of MAGE-3(271-285) substituted at these positions. We show that positions 278 and 280 are major proteasomal cleavage sites because they tolerate most amino acid substitutions. In contrast, the peptide bond after Val(279) is a minor cleavage site, influenced by both distal and proximal amino acid residues.
Mots-clé
Amino Acid Sequence, Animals, Antigens, Neoplasm, Cell Line, Cysteine Endopeptidases/metabolism, HLA-A Antigens/chemistry, HLA-A Antigens/metabolism, Humans, Hydrolysis, Mice, Molecular Sequence Data, Multienzyme Complexes/metabolism, Neoplasm Proteins/chemistry, Neoplasm Proteins/metabolism, Proteasome Endopeptidase Complex, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/11/2007 13:07
Dernière modification de la notice
20/08/2019 13:43
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