8VZ8
Crystal structure of mouse MAIT M2B TCR-MR1-5-OP-RU complex
Summary for 8VZ8
Entry DOI | 10.2210/pdb8vz8/pdb |
Descriptor | Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, Mouse MAIT TRAV1-TRAJ33 a-chain, ... (6 entities in total) |
Functional Keywords | mouse mait tcr recognition of mr1, immune system |
Biological source | Mus musculus (house mouse) More |
Total number of polymer chains | 4 |
Total formula weight | 93668.36 |
Authors | Ciacchi, L.,Rossjohn, J.,Awad, W. (deposition date: 2024-02-11, release date: 2024-04-10, Last modification date: 2024-05-08) |
Primary citation | Ciacchi, L.,Mak, J.Y.W.,Le, J.P.,Fairlie, D.P.,McCluskey, J.,Corbett, A.J.,Rossjohn, J.,Awad, W. Mouse mucosal-associated invariant T cell receptor recognition of MR1 presenting the vitamin B metabolite, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil. J.Biol.Chem., 300:107229-107229, 2024 Cited by PubMed Abstract: Mucosal-associated invariant T (MAIT) cells can elicit immune responses against riboflavin-based antigens presented by the evolutionary conserved MHC class I related protein, MR1. While we have an understanding of the structural basis of human MAIT cell receptor (TCR) recognition of human MR1 presenting a variety of ligands, how the semi-invariant mouse MAIT TCR binds mouse MR1-ligand remains unknown. Here, we determine the crystal structures of 2 mouse TRAV1-TRBV13-2 MAIT TCR-MR1-5-OP-RU ternary complexes, whose TCRs differ only in the composition of their CDR3β loops. These mouse MAIT TCRs mediate high affinity interactions with mouse MR1-5-OP-RU and cross-recognize human MR1-5-OP-RU. Similarly, a human MAIT TCR could bind mouse MR1-5-OP-RU with high affinity. This cross-species recognition indicates the evolutionary conserved nature of this MAIT TCR-MR1 axis. Comparing crystal structures of the mouse versus human MAIT TCR-MR1-5-OP-RU complexes provides structural insight into the conserved nature of this MAIT TCR-MR1 interaction and conserved specificity for the microbial antigens, whereby key germline-encoded interactions required for MAIT activation are maintained. This is an important consideration for the development of MAIT cell-based therapeutics that will rely on preclinical mouse models of disease. PubMed: 38537698DOI: 10.1016/j.jbc.2024.107229 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (3.45 Å) |
Structure validation
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