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Publication Abstract from PubMed

The molecular mechanism through which the interaction of a clonotypic alphabeta T-cell receptor (TCR) with a peptide-loaded major histocompatibility complex (p/MHC) leads to T-cell activation is not yet fully understood. Here we exploit a high-affinity TCR (B4.2.3) to examine the structural changes that accompany binding to its p/MHC ligand (P18-I10/H2-Dd). In addition to conformational changes in complementarity-determining regions (CDRs) of the TCR seen in comparison of unliganded and bound X-ray structures, NMR characterization of the TCR beta-chain dynamics reveals significant chemical shift effects in sites removed from the MHC-binding site. Remodelling of electrostatic interactions near the Cbeta H3 helix at the membrane-proximal face of the TCR, a region implicated in interactions with the CD3 co-receptor, suggests a possible role for an allosteric mechanism in TCR signalling. The contribution of these TCR residues to signal transduction is supported by mutagenesis and T-cell functional assays.

An allosteric site in the T-cell receptor Cbeta domain plays a critical signalling role.,Natarajan K, McShan AC, Jiang J, Kumirov VK, Wang R, Zhao H, Schuck P, Tilahun ME, Boyd LF, Ying J, Bax A, Margulies DH, Sgourakis NG Nat Commun. 2017 May 16;8:15260. doi: 10.1038/ncomms15260. PMID:28508865^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.