Imperial College London
Alternate

ProfessorXiao-NingXu

Faculty of Medicine, Department of Infectious Disease

Chair in Human Immunology
 
 
 
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Contact

 

+44 (0)20 3315 6558x.xu

 
 
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Assistant

 

Dr Victoria Male +44 (0)20 3315 3000

 
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Location

 

Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Jonsson:2016:10.1073/pnas.1513918113,
author = {Jonsson, P and Southcombe, JH and Santos, AM and Huo, J and Fernandes, RA and McColl, J and Lever, M and Evans, EJ and Hudson, A and Chang, VT and Hanke, T and Godkin, A and Dunne, PD and Horrocks, MH and Palayret, M and Screaton, GR and Petersen, J and Rossjohn, J and Fugger, L and Dushek, O and Xu, X-N and Davis, SJ and Klenerman, D},
doi = {10.1073/pnas.1513918113},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
pages = {5682--5687},
title = {Remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions},
url = {http://dx.doi.org/10.1073/pnas.1513918113},
volume = {113},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The αβ T-cell coreceptor CD4 enhances immune responses more than 1 million-fold in some assays, and yet the affinity of CD4 for its ligand, peptide-major histocompatibility class II (pMHC II) on antigen-presenting cells, is so weak that it was previously unquantifiable. Here, we report that a soluble form of CD4 failed to bind detectably to pMHC II in surface plasmon resonance-based assays, establishing a new upper limit for the solution affinity at 2.5 mM. However, when presented multivalently on magnetic beads, soluble CD4 bound pMHC II-expressing B cells, confirming that it is active and allowing mapping of the native coreceptor binding site on pMHC II. Whereas binding was undetectable in solution, the affinity of the CD4/pMHC II interaction could be measured in 2D using CD4- and adhesion molecule-functionalized, supported lipid bilayers, yielding a 2D Kd of ∼5,000 molecules/μm2. This value is two to three orders of magnitude higher than previously measured 2D Kd values for interacting leukocyte surface proteins. Calculations indicated, however, that CD4/pMHC II binding would increase rates of T-cell receptor (TCR) complex phosphorylation by threefold via the recruitment of Lck, with only a small, 2–20% increase in the effective affinity of the TCR for pMHC II. The affinity of CD4/pMHC II therefore seems to be set at a value that increases T-cell sensitivity by enhancing phosphorylation, without compromising ligand discrimination.
AU  - Jonsson,P
AU  - Southcombe,JH
AU  - Santos,AM
AU  - Huo,J
AU  - Fernandes,RA
AU  - McColl,J
AU  - Lever,M
AU  - Evans,EJ
AU  - Hudson,A
AU  - Chang,VT
AU  - Hanke,T
AU  - Godkin,A
AU  - Dunne,PD
AU  - Horrocks,MH
AU  - Palayret,M
AU  - Screaton,GR
AU  - Petersen,J
AU  - Rossjohn,J
AU  - Fugger,L
AU  - Dushek,O
AU  - Xu,X-N
AU  - Davis,SJ
AU  - Klenerman,D
DO  - 10.1073/pnas.1513918113
EP  - 5687
PY  - 2016///
SN  - 1091-6490
SP  - 5682
TI  - Remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions
T2  - Proceedings of the National Academy of Sciences of the United States of America
UR  - http://dx.doi.org/10.1073/pnas.1513918113
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000375977600057&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.pnas.org/content/113/20/5682/
UR  - http://hdl.handle.net/10044/1/33706
VL  - 113
ER  -
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