MAIT cell-MR1 reactivity is highly conserved across multiple divergent species

Area of Science:

• Immunology
• Comparative immunology
• T cell biology

Background:

• Mucosal-associated invariant T (MAIT) cells are unconventional T cells recognizing microbial metabolites via MR1 and TCR.
• MAIT TCRs and MR1 molecules are highly conserved across mammals.
• This conservation enables species-mismatched MR1-antigen tetramer use in comparative immunology.

Purpose of the Study:

• To assess the cross-reactivity patterns of species-mismatched MR1-antigen tetramers for MAIT cell identification.
• To characterize MAIT cell populations in various species using novel and existing MR1-antigen tetramers.

Main Methods:

• Development of novel cattle and pig MR1-antigen tetramers.
• Utilization of human, mouse, pig-tailed macaque, cattle, and pig MR1-antigen tetramers.
• Phenotypic identification of MAIT cells in sheep using species-mismatched tetramers.

Main Results:

• MR1-antigen tetramers identified MAIT cells across species with comparable specificity to species-matched tetramers.
• Subtle differences in staining characteristics were observed, affecting MAIT cell identification.
• Pig MR1-antigen tetramers identified MAIT cells in other species, though MAIT cells in pigs were difficult to detect.
• Species-mismatched tetramers identified MAIT cells in sheep in the absence of sheep-specific tetramers.

Conclusions:

• Species-mismatched MR1-antigen tetramers are validated tools for comparative immunology studies.
• Understanding the limitations and subtle differences in staining is crucial for accurate MAIT cell identification across species.