Journal article
Remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions
P Jönsson, JH Southcombe, A Mafalda Santos, J Huo, RA Fernandes, J McColl, M Lever, EJ Evans, A Hudson, VT Chang, T Hanke, A Godkin, PD Dunne, MH Horrocks, M Palayret, GR Screaton, J Petersen, J Rossjohn, L Fugger, O Dushek Show all
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2016
Abstract
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..
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Awarded by Royal Society
Funding Acknowledgements
We thank Professor P. A. van der Merwe and Dr. Marco Fritzsche for helpful comments on the manuscript and Dr. Hugh Reid for technical advice on pMHC II expression. This work was supported by the Wellcome Trust, the UK Medical Research Council, and the Swedish Research Council Grants 623-2014-6387 and 621-2014-3907 (to P.J.). O.D. is supported by the Sir Henry Dale Fellowship Grant 098363 jointly funded by the Wellcome Trust and the Royal Society.