Production of spliced peptides by the proteasome. (September 2019)

• Record Type: Journal Article
• Authors: Vigneron, Nathalie; Stroobant, Vincent; Ferrari, Violette; Abi Habib, Joanna; Van den Eynde, Benoit J.
• Is Part Of: Molecular immunology. Volume 113(2019:Sep.)
• Page Start: 93
• Page End: 102
• Publication Date: 2019-09
• Subjects: Proteasome -- CD8+ cytolytic T lymphocytes -- Peptide splicing -- Transpeptidation -- Antigenic peptides; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2018.03.030
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: Proteasome can splice peptide fragments originally distant in a parental protein. Spliced peptides can be recognized at the cell surface by CD8 + T cells. Peptide splicing occurs by transpeptidation inside the proteasome catalytic chamber. Splicing activity is not restricted to a given proteasome subtype, and was also observed with yeast proteasome. Spliced peptides seem to account for about 25% of the peptides presented by MHC class I molecules at the cell surface. Abstract: CD8 + cytolytic T lymphocytes are essential players of anti-tumor immune responses. On tumors, they recognize peptides of about 8-to-10 amino acids that generally result from the degradation of cellular proteins by the proteasome. Until a decade ago, these peptides were thought to solely correspond to linear fragments of proteins that were liberated after the hydrolysis of the peptide bonds located at their extremities. However, several examples of peptides containing two fragments originally distant in the protein sequence challenged this concept and demonstrated that proteasome could also splice peptides together by creating a new peptide bond between two distant fragments. Unexpectedly, peptide splicing emerges as an essential way to increase the peptide repertoire diversity as these spliced peptides were shown to represent up to 25% of the peptides presented on a cell by MHC class I. Here, we review the different steps that led to the discovery of peptide splicing by the proteasome as well as the lightening offered by the recent progresses of mass spectrometry and bioinformatics in the analysis of the spliced peptide repertoire.