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

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager 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.

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 Editor¹

Laura Sesma^*, Begoña Galocha^*, Miriam Vázquez^*, Anthony W. Purcell, Miguel Marcilla^*, James McCluskey and José A. López de Castro^2,*

^* Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Facultad de Ciencias, Universidad Autónoma, Madrid, Spain; and Departments of Biochemistry and Molecular Biology and Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia

Tapasin (Tpn) is a chaperone of the endoplasmic reticulum involved in peptide loading to MHC class I proteins. The influence of mouse Tpn (mTpn) on the HLA-B*2705-bound peptide repertoire was analyzed to characterize the species specificity of this chaperone. B*2705 was expressed on Tpn-deficient human 721.220 cells cotransfected with human (hTpn) or mTpn. The heterodimer to ₂-microglobulin-free H chain ratio on the cell surface was reduced with mTpn, suggesting lower B*2705 stability. The B*2705-bound peptide repertoires loaded with hTpn or mTpn shared 94–97% identity, although significant differences in peptide amount were observed in 16–17% of the shared ligands. About 3–6% of peptides were bound only with either hTpn or mTpn. Nonamers differentially bound with mTpn had less suitable anchor residues and bound B*2705 less efficiently in vitro than those loaded only with hTpn or shared nonamers. Decamers showed a different pattern: those found only with mTpn had similarly suitable residues as shared decamers and bound B*2705 with high efficiency. Peptides differentially presented by B*2705 on human or mouse cells showed an analogous pattern of residue suitability, suggesting that the effect of mTpn on B*2705 loading is comparable in both cell types. Thus, mTpn has quantitative and qualitative effects on the B*2705-bound peptide repertoire, impairing presentation of some suitable ligands and allowing others with suboptimal anchor residues and lower affinity to be presented. Our results favor a size-dependent peptide editing role of Tpn for HLA-B*2705 that is species-dependent and suboptimally performed, at least for nonamers, by mTpn.

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]

				T. Raine, D. Brown, P. Bowness, J. S. Hill Gaston, A. Moffett, J. Trowsdale, and R. L. Allen Consistent patterns of expression of HLA class I free heavy chains in healthy individuals and raised expression in spondyloarthropathy patients point to physiological and pathological roles Rheumatology, November 1, 2006; 45(11): 1338 - 1344. [Abstract] [Full Text] [PDF]