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(5): 107229, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38537698
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 CDR3ß 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ribitol
/
Histocompatibility Antigens Class I
/
Minor Histocompatibility Antigens
/
Mucosal-Associated Invariant T Cells
Limits:
Animals
/
Humans
Language:
En
Journal:
J Biol Chem
/
J. biol. chem
/
Journal of biological chemistry
Year:
2024
Document type:
Article
Affiliation country:
Australia
Country of publication:
United States