Selective loading of high-affinity peptides onto major histocompatibility complex class i molecules by the tapasin-erp57 heterodimer

ABSTRACT Major histocompatibility complex (MHC) class I glycoproteins bind peptides in the endoplasmic reticulum after incorporation into the peptide-loading complex, whose core is the

transporter associated with antigen processing. Other components are the chaperone calreticulin, the thiol oxidoreductase ERp57, and tapasin. Tapasin and ERp57 have been shown to exist in

the peptide-loading complex as a disulfide-linked heterodimer. Here, using a cell-free system, we demonstrate that although recombinant tapasin was ineffective in recruiting MHC class I

molecules and facilitating peptide binding, recombinant tapasin-ERp57 conjugates accomplished both of those functions and also 'edited' the repertoire of bound peptides to maximize

their affinity. Thus, the tapasin-ERp57 conjugate is the functional unit of the peptide-loading complex that generates MHC class I molecules with stably associated peptides. Access through

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CONTENT BEING VIEWED BY OTHERS STRUCTURE OF AN MHC I–TAPASIN–ERP57 EDITING COMPLEX DEFINES CHAPERONE PROMISCUITY Article Open access 14 September 2022 LIGHT CONTROL OF THE PEPTIDE-LOADING

COMPLEX SYNCHRONIZES ANTIGEN TRANSLOCATION AND MHC I TRAFFICKING Article Open access 30 March 2021 MOLECULAR BASIS OF MHC I QUALITY CONTROL IN THE PEPTIDE LOADING COMPLEX Article Open access

10 August 2022 CHANGE HISTORY * _ 13 JULY 2007 In the version of this article initially published online, the right side of Figure 1c was cut off. The error has been corrected for all

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Immunol. Methods_ 215, 71–80 (1998). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank D. Peaper for discussions and critical review of the manuscript; S. Mitchell,

R. Teel and A. Little for technical assistance; and N. Dometios for aid in preparing this manuscript. Supported by the Howard Hughes Medical Institute. AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, 06520-8011, Connecticut, USA Pamela A Wearsch & Peter

Cresswell Authors * Pamela A Wearsch View author publications You can also search for this author inPubMed Google Scholar * Peter Cresswell View author publications You can also search for

this author inPubMed Google Scholar CONTRIBUTIONS P.A.W. designed and implemented all experiments; P.A.W. and P.C. wrote the paper. CORRESPONDING AUTHOR Correspondence to Peter Cresswell.

ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Wearsch,

P., Cresswell, P. Selective loading of high-affinity peptides onto major histocompatibility complex class I molecules by the tapasin-ERp57 heterodimer. _Nat Immunol_ 8, 873–881 (2007).

https://doi.org/10.1038/ni1485 Download citation * Received: 19 March 2007 * Accepted: 06 June 2007 * Published: 01 July 2007 * Issue Date: August 2007 * DOI: https://doi.org/10.1038/ni1485

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