HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 47, 46461-46472, November 21, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/47/46461    most recent M308816200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sesma, L. Articles by de Castro, J. A. L. Search for Related Content PubMed PubMed Citation Articles by Sesma, L. Articles by de Castro, J. A. L. Social Bookmarking                      What's this?

Species-specific Differences in Proteasomal Processing and Tapasin-mediated Loading Influence Peptide Presentation by HLA-B27 in Murine Cells^*

Laura Sesma, Iñaki Alvarez, Miguel Marcilla, Alberto Paradela, and José A. López de Castro

From the Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Facultad de Ciencias, Universidad Autónoma, 28049 Madrid, Spain

Expression of HLA-B27 in murine cells has been used to establish animal models for human spondyloarthritis and for antigen presentation studies, but the effects of xenogeneic HLA-B27 expression on peptide presentation are little known. The issue was addressed in this study. HLA-B27-bound peptide repertoires from human and murine cells overlapped by 75–85%, indicating that many endogenous HLA-B27 ligands are generated and presented in both species. Of 20 differentially presented peptides that were sequenced, only 40% arose from obvious inter-species protein polymorphism, suggesting that differences in antigen processing-loading accounted for many species-specific ligands. Digestion of synthetic substrates with human and murine 20 S proteasomes revealed cleavage differences that accounted for or correlated with differential expression of particular peptides. One HLA-B27 ligand found only in human cells was similarly generated in vitro by human and murine proteasomes. Differential presentation correlated with significantly decreased amounts of this ligand in human tapasin-deficient cells reconstituted with murine tapasin, indicating that species-specific interactions between HLA-B27, tapasin, and/or other proteins in the peptide-loading complex influenced presentation of this peptide. Our results indicate that differences in proteasomal specificity and in interactions involving tapasin determine differential processing and presentation of a significant number of HLA-B27 ligands in human and murine cells.

Received for publication, August 11, 2003

^* This work was supported by grants SAF99/0055, PM99-0098, and SAF2002/00125 from the Ministry of Science and Technology, and 08.3/0005/2001.1 from the Comunidad Autónoma de Madrid. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 34-91-397-8050; Fax: 34-91-397-8087; E-mail: aldecastro{at}cbm.uam.es.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				V. Montserrat, B. Galocha, M. Marcilla, M. Vazquez, and J. A. Lopez de Castro HLA-B*2704, an Allotype Associated with Ankylosing Spondylitis, Is Critically Dependent on Transporter Associated with Antigen Processing and Relatively Independent of Tapasin and Immunoproteasome for Maturation, Surface Expression, and T Cell Recognition: Relationship to B*2705 and B*2706 J. Immunol., November 15, 2006; 177(10): 7015 - 7023. [Abstract] [Full Text] [PDF]

				V. Pasquetto, H.-H. Bui, R. Giannino, F. Mirza, J. Sidney, C. Oseroff, D. C. Tscharke, K. Irvine, J. R. Bennink, B. Peters, et al. HLA-A*0201, HLA-A*1101, and HLA-B*0702 Transgenic Mice Recognize Numerous Poxvirus Determinants from a Wide Variety of Viral Gene Products J. Immunol., October 15, 2005; 175(8): 5504 - 5515. [Abstract] [Full Text] [PDF]

				L. Sesma, B. Galocha, M. Vazquez, A. W. Purcell, M. Marcilla, J. McCluskey, and J. A. L. de Castro Qualitative and Quantitative Differences in Peptides Bound to HLA-B27 in the Presence of Mouse versus Human Tapasin Define a Role for Tapasin as a Size-Dependent Peptide Editor J. Immunol., June 15, 2005; 174(12): 7833 - 7844. [Abstract] [Full Text] [PDF]

				H. R. Turnquist, J. L. Petersen, S. E. Vargas, M. M. McIlhaney, E. Bedows, W. E. Mayer, A. G. Grandea III, L. Van Kaer, and J. C. Solheim The Ig-Like Domain of Tapasin Influences Intermolecular Interactions J. Immunol., March 1, 2004; 172(5): 2976 - 2984. [Abstract] [Full Text] [PDF]