The University of Southampton
University of Southampton Institutional Repository

Peptide-independent stabilization of MHC class I molecules breaches cellular quality control

Record type: Article

The intracellular trafficking of major histocompatibility complex class I (MHC-I) proteins is directed by three quality control mechanisms that test for their structural integrity, which is correlated to the binding of high-affinity antigenic peptide ligands. To investigate which molecular features of MHC-I these quality control mechanisms detect, we have followed the hypothesis that suboptimally loaded MHC-I molecules are characterized by their conformational mobility in the F-pocket region of the peptide-binding site. We have created a novel variant of an MHC-I protein, Kb-Y84C, in which two ?-helices in this region are linked by a disulfide bond that mimics the conformational and dynamic effects of bound high-affinity peptide. Kb-Y84C shows a remarkable increase in the binding affinity to its light chain, beta-2 microglobulin (?2m), and bypasses all three cellular quality control steps. Our data demonstrate (1) that coupling between peptide and ?2m binding to the MHC-I heavy chain is mediated by conformational dynamics; (2) that the folded conformation of MHC-I, supported by ?2m, plays a decisive role in passing the ER-to-cell-surface transport quality controls; and (3) that ?2m association is also tested by the cell surface quality control that leads to MHC-I endocytosis.

Full text not available from this repository.


Hein, Z., Uchtenhagen, H., Abualrous, E.T., Saini, S.K., Janssen, L., Van Hateren, A., Wiek, C., Hanenberg, H., Momburg, F., Achour, A., Elliott, T., Springer, S. and Boulanger, D. (2014) Peptide-independent stabilization of MHC class I molecules breaches cellular quality control Journal of Cell Science, 127, (13), pp. 2885-2897. (doi:10.1242/jcs.145334). (PMID:24806963).

More information

e-pub ahead of print date: 7 May 2014
Published date: 1 July 2014
Keywords: antigen presentation, endocytosis, major histocompatibility complex, ER quality control
Organisations: Cancer Sciences


Local EPrints ID: 368149
ISSN: 0021-9533
PURE UUID: dedcc22a-ea4f-4389-8a2e-b7fa8d4e722c
ORCID for T. Elliott: ORCID iD

Catalogue record

Date deposited: 19 Aug 2014 10:06
Last modified: 18 Jul 2017 01:51

Export record



Author: Z. Hein
Author: H. Uchtenhagen
Author: E.T. Abualrous
Author: S.K. Saini
Author: L. Janssen
Author: A. Van Hateren
Author: C. Wiek
Author: H. Hanenberg
Author: F. Momburg
Author: A. Achour
Author: T. Elliott ORCID iD
Author: S. Springer
Author: D. Boulanger

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.