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Sökning: onr:"swepub:oai:lup.lub.lu.se:cb93631a-5054-4a9b-af3b-9edf38f108cf" > Remarkably low affi...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005014naa a2200649 4500
001oai:lup.lub.lu.se:cb93631a-5054-4a9b-af3b-9edf38f108cf
003SwePub
008170130s2016 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/cb93631a-5054-4a9b-af3b-9edf38f108cf2 URI
0247 a https://doi.org/10.1073/pnas.15139181132 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 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
2451 0a Remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions
264 c 2016-04-25
264 1b 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 7a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe
650 7a 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
7001 a Southcombe, Jennifer H.u University of Oxford4 aut
7001 a Mafalda Santos, Anau University of Oxford4 aut
7001 a Huo, Jiandongu University of Oxford4 aut
7001 a Fernandes, Ricardo A.u University of Oxford4 aut
7001 a McColl, Jamesu University of Cambridge4 aut
7001 a Lever, Melissau University of Oxford4 aut
7001 a Evans, Edward J.u University of Oxford4 aut
7001 a Hudson, Alexanderu University of Oxford4 aut
7001 a Chang, Veronica T.u University of Oxford4 aut
7001 a Hanke, Tomášu University of Oxford4 aut
7001 a Godkin, Andrewu Cardiff University4 aut
7001 a Dunne, Paul D.u University of Cambridge4 aut
7001 a Horrocks, Mathew H.u University of Cambridge4 aut
7001 a Palayret, Matthieuu University of Cambridge4 aut
7001 a Screaton, Gavin R.u University of Oxford4 aut
7001 a Petersen, Janu Monash University4 aut
7001 a Rossjohn, Jamieu Cardiff University,Monash University4 aut
7001 a Fugger, Larsu University of Oxford4 aut
7001 a Dushek, Omeru University of Oxford4 aut
7001 a Xu, Xiao Ningu University of Oxford4 aut
7001 a Davis, Simon J.u University of Oxford4 aut
7001 a Klenerman, Davidu University of Cambridge4 aut
7102 a Fysikalisk kemib Enheten för fysikalisk och teoretisk kemi4 org
7730 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
7730 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
8564 u http://dx.doi.org/10.1073/pnas.1513918113y FULLTEXT
8564 u https://www.pnas.org/content/pnas/113/20/5682.full.pdf
8564 8u https://lup.lub.lu.se/record/cb93631a-5054-4a9b-af3b-9edf38f108cf
8564 8u https://doi.org/10.1073/pnas.1513918113

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