7llj
Inhibitory immune receptor protein complex
Structural highlights
FunctionHMR1_HUMAN Has antigen presentation function. Involved in the development and expansion of a small population of T-cells expressing an invariant T-cell receptor alpha chain called mucosal-associated invariant T-cells (MAIT). MAIT cells are preferentially located in the gut lamina propria and therefore may be involved in monitoring commensal flora or serve as a distress signal. Expression and MAIT cell recognition seem to be ligand-dependent.[1] Publication Abstract from PubMedUnlike conventional alphabeta T cells, gammadelta T cells typically recognize nonpeptide ligands independently of major histocompatibility complex (MHC) restriction. Accordingly, the gammadelta T cell receptor (TCR) can potentially recognize a wide array of ligands; however, few ligands have been described to date. While there is a growing appreciation of the molecular bases underpinning variable (V)delta1(+) and Vdelta2(+) gammadelta TCR-mediated ligand recognition, the mode of Vdelta3(+) TCR ligand engagement is unknown. MHC class I-related protein, MR1, presents vitamin B metabolites to alphabeta T cells known as mucosal-associated invariant T cells, diverse MR1-restricted T cells, and a subset of human gammadelta T cells. Here, we identify Vdelta1/2(-) gammadelta T cells in the blood and duodenal biopsy specimens of children that showed metabolite-independent binding of MR1 tetramers. Characterization of one Vdelta3Vgamma8 TCR clone showed MR1 reactivity was independent of the presented antigen. Determination of two Vdelta3Vgamma8 TCR-MR1-antigen complex structures revealed a recognition mechanism by the Vdelta3 TCR chain that mediated specific contacts to the side of the MR1 antigen-binding groove, representing a previously uncharacterized MR1 docking topology. The binding of the Vdelta3(+) TCR to MR1 did not involve contacts with the presented antigen, providing a basis for understanding its inherent MR1 autoreactivity. We provide molecular insight into antigen-independent recognition of MR1 by a Vdelta3(+) gammadelta TCR that strengthens an emerging paradigm of antibody-like ligand engagement by gammadelta TCRs. Recognition of the antigen-presenting molecule MR1 by a Vdelta3(+) gammadelta T cell receptor.,Rice MT, von Borstel A, Chevour P, Awad W, Howson LJ, Littler DR, Gherardin NA, Le Nours J, Giles EM, Berry R, Godfrey DI, Davey MS, Rossjohn J, Gully BS Proc Natl Acad Sci U S A. 2021 Dec 7;118(49):e2110288118. doi: , 10.1073/pnas.2110288118. PMID:34845016[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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