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Post-Translational Peptide Splicing and T Cell Responses

Research output: Contribution to journalArticle

Michele Mishto, Juliane Liepe

Original languageEnglish
Early online date19 Aug 2017
Accepted/In press26 Jul 2017
E-pub ahead of print19 Aug 2017


King's Authors


CD8+ T cell specificity depends on the recognition of MHC class I–epitope complexes at the cell surface. These epitopes are mainly produced via degradation of proteins by the proteasome, generating fragments of the original sequence. However, it is now clear that proteasomes can produce a significant portion of epitopes by reshuffling the antigen sequence, thus expanding the potential antigenic repertoire. MHC class I-restricted spliced epitopes have been described in tumors and infections, suggesting an unpredicted relevance of these peculiar peptides. We review current knowledge about proteasome-catalyzed peptide splicing (PCPS), the emerging rules governing this process, and the potential implications for our understanding and therapeutic use of CD8+ T cells, as well as mechanisms generating other non-canonical antigenic epitopes targeted by the T cell response.

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