Differences in the molecular signatures of mucosal-associated invariant T cells and conventional T cells

Mucosal-associated invariant T (MAIT) cells exhibit different characteristics from those of TCR alpha 7.2(-) conventional T cells. They play important roles in various inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease. MAIT cells express a single T cell receptor alpha chain, TCR alpha 7.2 segment associated with J alpha 33 and CDR3 with fixed length, which recognizes bacteria-derived vitamin B metabolites. However, the characteristics of MAIT cells and TCR alpha 7.2(+) CD161(-) T cells have never been compared. Here, we performed RNA sequencing to compare the properties of MAIT cells, TCR alpha 7.2(-) conventional T cells and TCR alpha 7.2(+) CD161(-) T cells. Genome-wide transcriptomes of MAIT cells, TCR alpha 7.2(-) conventional T cells, and TCR alpha 7.2(+) CD161(-) T cells were compared and analyzed using causal network analysis. This is the first report comparing the transcriptomes of MAIT cells, TCR alpha 7.2(-) conventional T cells and TCR alpha 7.2(+) CD161(-) T cells. We also identified the predominant signaling pathways of MAIT cells, which differed from those of TCR alpha 7.2(-) conventional T cells and TCR alpha 7.2(+) CD161(-) T cells, through a gene set enrichment test and upstream regulator analysis and identified the genes responsible for the characteristic MAIT cell phenotypes. Our study advances the complete understanding of MAIT biology.