4L8S

Crystal structure of a human Valpha7.2/Vbeta13.3 MAIT TCR in complex with bovine MR1

Summary for 4L8S

• Entry DOI: 10.2210/pdb4l8s/pdb
• Related: 4IIQ 4L9L
• Descriptor: Muccosal Associated Invariant T Cell Receptor alpha chain, Muccosal Associated Invariant T Cell Receptor beta chain, Beta-2-microglobulin, MHC class I-related protein, ... (5 entities in total)
• Functional Keywords: immunoglobulin domain, mhc-class i, antigen presentation, antigen recognition, antigen, cell membrane, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P01888
• Total number of polymer chains: 3
• Total formula weight: 97290.92

Authors

Lopez-Sagaseta, J.,Adams, E.J. (deposition date: 2013-06-17, release date: 2013-10-16, Last modification date: 2017-08-23)

Primary citation

Lopez-Sagaseta, J.,Dulberger, C.L.,McFedries, A.,Cushman, M.,Saghatelian, A.,Adams, E.J.
MAIT Recognition of a Stimulatory Bacterial Antigen Bound to MR1.
J.Immunol., 191:5268-5277, 2013

PubMed Abstract: MR1-restricted mucosal-associated invariant T (MAIT) cells represent a subpopulation of αβ 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 CDR3α and CDR3β 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 CDR2β and CDR3β 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 Vβ usage or CDR3β sequences.

PubMed: 24108697
DOI: 10.4049/jimmunol.1301958

Experimental method

X-RAY DIFFRACTION (2.9 Å)