PDBsum entry 4lcc

Immune system

PDB id: 4lcc

Contents

Protein chains

341 a.a.

157 a.a.

238 a.a.

Ligands

1XL

SO4 ×4

Waters ×1

References listed in PDB file

Key reference

• Title: Mait recognition of a stimulatory bacterial antigen bound to mr1.
• Authors: J.López-Sagaseta, C.L.Dulberger, A.Mcfedries, M.Cushman, A.Saghatelian, E.J.Adams.
• Ref.: J Immunol, 2013, 191, 5268-5277. [DOI no: 10.4049/jimmunol.1301958]
• PubMed id: 24108697

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.