4l9l | pdb_00004l9l
Crystal structure of a human Valpha7.2/Vbeta13.2 MAIT TCR in complex with bovine MR1
Structural highlights
FunctionPublication Abstract from PubMedMR1-restricted mucosal-associated invariant T (MAIT) cells represent a subpopulation of alphabeta T cells with innate-like properties and limited TCR diversity. MAIT cells are of interest because of their reactivity against bacterial and yeast species, suggesting that they play a role in defense against pathogenic microbes. Despite the advances in understanding MAIT cell biology, the molecular and structural basis behind their ability to detect MR1-Ag complexes is unclear. In this study, we present our structural and biochemical characterization of MAIT TCR engagement of MR1 presenting an Escherichia coli-derived stimulatory ligand, rRL-6-CH2OH, previously found in Salmonella typhimurium. We show a clear enhancement of MAIT TCR binding to MR1 due to the presentation of this ligand. Our structure of a MAIT TCR/MR1/rRL-6-CH2OH complex shows an evolutionarily conserved binding orientation, with a clear role for both the CDR3alpha and CDR3beta loops in recognizing the rRL-6-CH2OH stimulatory ligand. We also present two additional xenoreactive MAIT TCR/MR1 complexes that recapitulate the docking orientation documented previously, despite having variation in the CDR2beta and CDR3beta loop sequences. Our data support a model by which MAIT TCRs engage MR1 in a conserved fashion, with their binding affinities modulated by the nature of the MR1-presented Ag or diversity introduced by alternate Vbeta usage or CDR3beta sequences. MAIT Recognition of a Stimulatory Bacterial Antigen Bound to MR1.,Lopez-Sagaseta J, Dulberger CL, McFedries A, Cushman M, Saghatelian A, Adams EJ J Immunol. 2013 Nov 15;191(10):5268-77. doi: 10.4049/jimmunol.1301958. Epub 2013 , Oct 9. PMID:24108697[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
