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An Antigen Produced by Splicing of Noncontiguous Peptides in the Reverse Order
Edus H. Warren,1,2Nathalie J. Vigneron,4,5*Marc A. Gavin,1,3Pierre G. Coulie,5Vincent Stroobant,4,5Alexandre Dalet,4,5Scott S. Tykodi,1,2Suzanne M. Xuereb,1Jeffrey K. Mito,1Stanley R. Riddell,1,2Benoît J. Van den Eynde4,5
CD8-positive T lymphocytes recognize peptides that are usuallyderived from the degradation of cellular proteins and are presentedby class I molecules of the major histocompatibility complex.Here we describe a human minor histocompatibility antigen createdby a polymorphism in the SP110 nuclear phosphoprotein gene.The antigenic peptide comprises two noncontiguous SP110 peptidesegments spliced together in reverse order to that in whichthey occur in the predicted SP110 protein. The antigenic peptidecould be produced in vitro by incubation of precursor peptideswith highly purified 20S proteasomes. Cutting and splicing probablyoccur within the proteasome by transpeptidation.
1 Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. 2 Department of Medicine, University of Washington, Seattle, WA 98195, USA. 3 Department of Immunology, University of Washington, Seattle, WA 98195, USA. 4 Ludwig Institute for Cancer Research, Brussels Branch, B-1200 Brussels, Belgium. 5 Cellular Genetics Unit, Institute of Cellular Pathology, Université Catholique de Louvain, B-1200 Brussels, Belgium.
* Present address: Yale University School of Medicine, Sectionof Immunobiology, New Haven, CT 06510, USA.
To whom correspondence should be addressed. E-mail: benoit.vandeneynde{at}bru.licr.org
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