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Published Online March 4, 2004
Science DOI: 10.1126/science.1095522

Reports

Submitted on January 12, 2004
Accepted on February 25, 2004

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 3, Pierre van der Bruggen 1, Thierry Boon 1, Benoît J. Van den Eynde 1*

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, Liège, Belgium.
3 Ludwig Institute for Cancer Research and Cellular Genetics Unit, Université de Louvain, B-1200 Brussels, Belgium; Present address: GlaxoSmithKline Biologicals, Rixensart, Belgium.

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

CD8 T lymphocytes recognize peptides of 8-10 amino acids presented by class I molecules of the major histocompatibility complex. Here CD8 T lymphocytes were found to recognize on melanoma cells a nonameric peptide that comprises two non-contiguous segments of melanocytic protein gp100. The production of this peptide involves 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 function of the proteasome in producing antigenic peptides.


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