An Antigen Produced by Splicing of Noncontiguous Peptides in the Reverse Order

American Association for the Advancement of Science (AAAS) - Tập 313 Số 5792 - Trang 1444-1447 - 2006
Edus H. Warren1,2,3,4,5, Nathalie Vigneron1,2,3,4,5, Marc A. Gavin1,2,4,5, Pierre G. Coulie1,2,3,4,5, Vincent Stroobant1,2,3,4,5, Alexandre Dalet1,2,3,4,5, Scott S. Tykodi1,2,3,4,5, Suzanne M. Xuereb1,2,3,4,5, Jeffrey K. Mito1,2,3,4,5, Stanley R. Riddell1,2,3,4,5, Benoı̂t J. Van den Eynde1,2,3,4,5
1Cellular Genetics Unit, Institute of Cellular Pathology, Université Catholique de Louvain, B-1200 Brussels, Belgium.
2Department of Immunology, University of Washington, Seattle, WA 98195, USA.
3Department of Medicine, University of Washington, Seattle, WA 98195, USA
4Ludwig Institute for Cancer Research Brussels Branch, B-1200 Brussels, Belgium
5Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA

Tóm tắt

CD8-positive T lymphocytes recognize peptides that are usually derived from the degradation of cellular proteins and are presented by class I molecules of the major histocompatibility complex. Here we describe a human minor histocompatibility antigen created by a polymorphism in the SP110 nuclear phosphoprotein gene. The antigenic peptide comprises two noncontiguous SP110 peptide segments spliced together in reverse order to that in which they occur in the predicted SP110 protein. The antigenic peptide could be produced in vitro by incubation of precursor peptides with highly purified 20 S proteasomes. Cutting and splicing probably occur within the proteasome by transpeptidation.

Từ khóa


Tài liệu tham khảo

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We thank L. Pilotte for excellent assistance J. Chapiro and B. Guillaume for providing purified proteasomes and T. Boon and J. Chapiro for critical reading of the manuscript. Supported by a Lilly Clinical Investigator Award from the Damon Runyon Cancer Research Foundation (E.H.W.) and by grants from the NIH to E.H.W. (CA106512) and to S.R.R. (CA18029) the Belgian Programme on Interuniversity Poles of Attraction the Fonds National de la Recherche Scientifique (FNRS Belgium) the Fondation Contre le Cancer (Belgium) the Fonds Maisin (Belgium) and the Fondation Salus Sanguinis (Belgium). N.J.V. and A.D. were supported by Télévie grants from the FNRS (Belgium).