Protein cleavage by the proteasome supplies peptides that are loaded onto major histocompatibility complex class I molecules and are presented as epitopes to CD8+ T cells. In Science, Liepe et al. investigate the human 'immunopeptidome' presented by HLA-I and report that proteasome-generated spliced peptides contribute roughly one fourth of the antigenic epitope repertoire displayed on the cell surface. Spliced peptide epitopes are produced by lymphoblastoid cell lines and primary human fibroblasts. Remarkably, some self antigens are presented only as cis-spliced epitopes that are derived by deletion of intervening amino acids to obtain the final 9- to 12-residue peptide. Although the rules for how proteasomes generate spliced peptides remain to be delineated, such processing can vastly increase the repertoire of peptides surveyed by CD8+ T cells. Whether infection or inflammation alters this process likewise remains unknown.

Science 354, 354–358 (2016)