Reciprocal TCR-CD3 and CD4 Engagement of a Nucleating pMHCII Stabilizes a Functional Receptor Macrocomplex
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Univ Arizona, Coll Med, Dept ImmunobiolUniv Arizona, Coll Med
Univ Arizona, Coll Med, Arizona Ctr Aging
Univ Arizona, Coll Med, Canc Ctr
Issue Date
2018-01
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CELL PRESSCitation
Reciprocal TCR-CD3 and CD4 Engagement of a Nucleating pMHCII Stabilizes a Functional Receptor Macrocomplex 2018, 22 (5):1263 Cell ReportsJournal
Cell ReportsRights
© 2017 The Author(s). This is an open access article under the CC BY-NC-ND license.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
CD4(+) T cells convert the time that T cell receptors (TCRs) interact with peptides embedded within class II major histocompatibility complex molecules (pMHCII) into signals that direct cell-fate decisions. In principle, TCRs relay information to intracellular signaling motifs of the associated CD3 subunits, while CD4 recruits the kinase Lck to those motifs upon coincident detection of pMHCII. But the mechanics by which this occurs remain enigmatic. In one model, the TCR and CD4 bind pMHCII independently, while in another, CD4 interacts with a composite surface formed by the TCR-CD3 complex bound to pMHCII. Here, we report that the duration of TCR-pMHCII interactions impact CD4 binding to MHCII. In turn, CD4 increases TCR confinement to pMHCII via reciprocal interactions involving membrane distal and proximal CD4 ectodomains. The data suggest that a precisely assembled macrocomplex functions to reliably convert TCR-pMHCII confinement into reproducible signals that orchestrate adaptive immunity.Note
UA Open Access Publishing Fund.ISSN
22111247PubMed ID
29386113Version
Final published versionSponsors
Cancer Center Support Grant [CCSG-CA 023074]; Pew Charitable Trusts; University of Arizona College of Medicine; Bio5 Institute; NIH/NIAID [R01AI101053]Additional Links
http://linkinghub.elsevier.com/retrieve/pii/S2211124717319563ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2017.12.104
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Except where otherwise noted, this item's license is described as © 2017 The Author(s). This is an open access article under the CC BY-NC-ND license.
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