9MS0

Structure of human neonatal MAIT A2 TCR in complex with human MR1-5-OP-RU

Summary for 9MS0

• Entry DOI: 10.2210/pdb9ms0/pdb
• Descriptor: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, A2-TRAV1-2-TRAJ12, ... (6 entities in total)
• Functional Keywords: antigen presentation, mait cells, t cell receptor, mr1, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 93668.61

Authors

Awad, W.,Rossjohn, J. (deposition date: 2025-01-09, release date: 2026-01-14, Last modification date: 2026-08-26)

Primary citation

Kain, D.,Awad, W.,McElfresh, G.W.,Cansler, M.,Swarbrick, G.M.,Chan Yew Poa, K.,McNeice, C.,Boggy, G.,Rott, K.H.,Null, M.D.,Lewinsohn, D.M.,Rossjohn, J.,Bimber, B.N.,Lewinsohn, D.A.
Human neonatal MR1T cells have more diverse TCR repertoires but reduced bacterial recognition than adult MR1T cells.
Nat Commun, 17:-, 2026

PubMed Abstract: Bacterial sepsis is a leading cause of neonatal mortality. Pro-inflammatory MR1-restricted T (MR1T) cells may help protect from sepsis by recognizing bacterial pathogens producing the canonical MR1 antigen 5-OP-RU. Most adult MR1T cells are mucosal-associated invariant T (MAIT) cells expressing a semi-invariant TCRα, while neonatal MR1T cells express diverse TCRα chains. Here, we perform combined single-cell RNA-sequencing and TCR repertoire analyses on MR1/5-OP-RU tetramer-positive cells from neonatal cord blood (CB) and adult blood. Compared to adult MR1T cells, CB MR1T cells exhibit greater TCR diversity, reduced cytotoxic and proinflammatory gene expression, diminished bacterial recognition and reduced binding to MR1/5-OP-RU. Structural analysis of a CB MAIT TCR reveals decreased β chain contribution to the TCR-MR1 interface relative to an adult MAIT TCR. These findings demonstrate developmental stage-specific differences in MR1T cell repertoire, function and MAIT TCR structure with implications for neonatal sepsis.

PubMed: 42373629
DOI: 10.1038/s41467-026-74998-7

Experimental method

X-RAY DIFFRACTION (2.52 Å)