7zt3 | pdb_00007zt3
Structure of E8 TCR in complex in human MR1 K43A
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 PubMedMucosal-associated invariant T (MAIT) cells use canonical semi-invariant T cell receptors (TCR) to recognize microbial riboflavin precursors displayed by the antigen-presenting molecule MR1. The extent of MAIT TCR crossreactivity toward physiological, microbially unrelated antigens remains underexplored. We describe MAIT TCRs endowed with MR1-dependent reactivity to tumor and healthy cells in the absence of microbial metabolites. MAIT cells bearing TCRs crossreactive toward self are rare but commonly found within healthy donors and display T-helper-like functions in vitro. Experiments with MR1-tetramers loaded with distinct ligands revealed significant crossreactivity among MAIT TCRs both ex vivo and upon in vitro expansion. A canonical MAIT TCR was selected on the basis of extremely promiscuous MR1 recognition. Structural and molecular dynamic analyses associated promiscuity to unique TCRbeta-chain features that were enriched within self-reactive MAIT cells of healthy individuals. Thus, self-reactive recognition of MR1 represents a functionally relevant indication of MAIT TCR crossreactivity, suggesting a potentially broader role of MAIT cells in immune homeostasis and diseases, beyond microbial immunosurveillance. Promiscuous recognition of MR1 drives self-reactive mucosal-associated invariant T cell responses.,Chancellor A, Alan Simmons R, Khanolkar RC, Nosi V, Beshirova A, Berloffa G, Colombo R, Karuppiah V, Pentier JM, Tubb V, Ghadbane H, Suckling RJ, Page K, Crean RM, Vacchini A, De Gregorio C, Schaefer V, Constantin D, Gligoris T, Lloyd A, Hock M, Srikannathasan V, Robinson RA, Besra GS, van der Kamp MW, Mori L, Calogero R, Cole DK, De Libero G, Lepore M J Exp Med. 2023 Sep 4;220(9):e20221939. doi: 10.1084/jem.20221939. Epub 2023 Jun , 29. PMID:37382893[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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