Sökning: onr:"swepub:oai:lup.lub.lu.se:cb93631a-5054-4a9b-af3b-9edf38f108cf" > Remarkably low affi...
Fältnamn | Indikatorer | Metadata |
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000 | 05014naa a2200649 4500 | |
001 | oai:lup.lub.lu.se:cb93631a-5054-4a9b-af3b-9edf38f108cf | |
003 | SwePub | |
008 | 170130s2016 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/cb93631a-5054-4a9b-af3b-9edf38f108cf2 URI |
024 | 7 | a https://doi.org/10.1073/pnas.15139181132 DOI |
040 | a (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Jönsson, Peteru Lund University,Lunds universitet,Fysikalisk kemi,Enheten för fysikalisk och teoretisk kemi,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Physical Chemistry,Physical and theoretical chemistry,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,University of Cambridge4 aut0 (Swepub:lu)ftf-pej |
245 | 1 0 | a Remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions |
264 | c 2016-04-25 | |
264 | 1 | b Proceedings of the National Academy of Sciences,c 2016 |
300 | a 6 s. | |
520 | a 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. | |
650 | 7 | a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng |
653 | a Adhesion | |
653 | a Binding equilibrium and kinetics | |
653 | a Protein interactions | |
653 | a T-cell activation | |
653 | a TCR phosphorylation | |
700 | 1 | a Southcombe, Jennifer H.u University of Oxford4 aut |
700 | 1 | a Mafalda Santos, Anau University of Oxford4 aut |
700 | 1 | a Huo, Jiandongu University of Oxford4 aut |
700 | 1 | a Fernandes, Ricardo A.u University of Oxford4 aut |
700 | 1 | a McColl, Jamesu University of Cambridge4 aut |
700 | 1 | a Lever, Melissau University of Oxford4 aut |
700 | 1 | a Evans, Edward J.u University of Oxford4 aut |
700 | 1 | a Hudson, Alexanderu University of Oxford4 aut |
700 | 1 | a Chang, Veronica T.u University of Oxford4 aut |
700 | 1 | a Hanke, Tomášu University of Oxford4 aut |
700 | 1 | a Godkin, Andrewu Cardiff University4 aut |
700 | 1 | a Dunne, Paul D.u University of Cambridge4 aut |
700 | 1 | a Horrocks, Mathew H.u University of Cambridge4 aut |
700 | 1 | a Palayret, Matthieuu University of Cambridge4 aut |
700 | 1 | a Screaton, Gavin R.u University of Oxford4 aut |
700 | 1 | a Petersen, Janu Monash University4 aut |
700 | 1 | a Rossjohn, Jamieu Cardiff University,Monash University4 aut |
700 | 1 | a Fugger, Larsu University of Oxford4 aut |
700 | 1 | a Dushek, Omeru University of Oxford4 aut |
700 | 1 | a Xu, Xiao Ningu University of Oxford4 aut |
700 | 1 | a Davis, Simon J.u University of Oxford4 aut |
700 | 1 | a Klenerman, Davidu University of Cambridge4 aut |
710 | 2 | a Fysikalisk kemib Enheten för fysikalisk och teoretisk kemi4 org |
773 | 0 | t Proceedings of the National Academy of Sciences of the United States of Americad : Proceedings of the National Academy of Sciencesg 113:20, s. 5682-5687q 113:20<5682-5687x 0027-8424 |
773 | 0 | t Proceedings of the National Academy of Sciencesd : Proceedings of the National Academy of Sciencesg 113:20, s. 5682-5687q 113:20<5682-5687x 1091-6490 |
856 | 4 | u http://dx.doi.org/10.1073/pnas.1513918113y FULLTEXT |
856 | 4 | u https://www.pnas.org/content/pnas/113/20/5682.full.pdf |
856 | 4 8 | u https://lup.lub.lu.se/record/cb93631a-5054-4a9b-af3b-9edf38f108cf |
856 | 4 8 | u https://doi.org/10.1073/pnas.1513918113 |
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