A large fraction of HLA class I ligands are proteasome-generated spliced peptides

• Autores: Juliane Liepe, Fabio Marino, John Sidney, Anita Jeko
• Localización: Science, ISSN 0036-8075, Vol. 354, Nº 6310, 2016, págs. 355-358
• Idioma: inglés
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• Resumen

  • The proteasome generates the epitopes presented on human leukocyte antigen (HLA) class I molecules that elicit CD8+ T cell responses. Reports of proteasome-generated spliced epitopes exist, but they have been regarded as rare events. Here, however, we show that the proteasome-generated spliced peptide pool accounts for one-third of the entire HLA class I immunopeptidome in terms of diversity and one-fourth in terms of abundance. This pool also represents a unique set of antigens, possessing particular and distinguishing features. We validated this observation using a range of complementary experimental and bioinformatics approaches, as well as multiple cell types. The widespread appearance and abundance of proteasome-catalyzed peptide splicing events has implications for immunobiology and autoimmunity theories and may provide a previously untapped source of epitopes for use in vaccines and cancer immunotherapy.