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Originally published in Science Express on 4 March 2004
Science 23 April 2004:
Vol. 304. no. 5670, pp. 587 - 590
DOI: 10.1126/science.1095522
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Reports

An Antigenic Peptide Produced by Peptide Splicing in the Proteasome

Nathalie Vigneron,1* Vincent Stroobant,1* Jacques Chapiro,1 Annie Ooms,2 Gérard Degiovanni,2 Sandra Morel,1{dagger} Pierre van der Bruggen,1 Thierry Boon,1 Benoît J. Van den Eynde1{ddagger}

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 gp100PMEL17. 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.

1 Ludwig Institute for Cancer Research and Cellular Genetics Unit, Université de Louvain, B-1200 Brussels, Belgium.
2 Laboratoire de Chirurgie Expérimentale, Université de Liège, B-4000 Liège, Belgium.



* These authors contributed equally to this work.

{dagger} Present address: GlaxoSmithKline Biologicals, Rue de l'Institut 89, 1330 Rixensart, Belgium.

{ddagger} To whom correspondence should be addressed. E-mail: benoit.vandeneynde{at}bru.licr.org

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