An Antigenic Peptide Produced by Peptide Splicing in the Proteasome

CD8 T lymphocytes recognize peptides of 8 to 10 amino acids presented by class I molecules of the major histocompatibility complex. Here, CD8 T lymphocytes were found to recognize a nonameric peptide on melanoma cells that comprises two noncontiguous segments of melanocytic glycoprotein$gp100^{PMEL17}$. The production of this peptide involves the excision of four amino acids and splicing of the fragments. This process was reproduced in vitro by incubating a precursor peptide of 13 amino acids with highly purified proteasomes. Splicing appears to occur by transpeptidation involving an acyl-enzyme intermediate. Our results reveal an unanticipated aspect of the proteasome function of producing antigenic peptides.