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

Details

Serval ID
serval:BIB_15032
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Amino acid identity and/or position determines the proteasomal cleavage of the HLA-A*0201-restricted peptide tumor antigen MAGE-3271-279.
Journal
Journal of Biological Chemistry
Author(s)
Miconnet I., Servis C., Cerottini J.C., Romero P., Lévy F.
ISSN
0021-9258[print], 0021-9258[linking]
Publication state
Published
Issued date
2000
Volume
275
Number
35
Pages
26892-26897
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
19/11/2007 12:07
Last modification date
20/08/2019 12:43
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