Ulcerative colitis (UC) is an increasingly prevalent form of inflammatory bowel disease. UC is characterized by a chronic T cell mediated inflammation of colonic mucosa that can cause bloody diarrhea, abdominal and rectal pain, weight loss and fatigue. Currently, it is thought that a confluence of immune dysregulation, genetics, the microbiome, and environmental factors contribute to the colonic inflammation. One immune cell subtype that may be a “link” between microbial antigens, environmental factors and chronic inflammation are the mucosal associated invariant T (MAIT) cells as they represent a significant proportion of CD8+ T cells in peripheral blood and gut mucosa. We are in the process of examining a cohort of 24 newly diagnosed UC patients, prior to treatment, using MR1 tetramers and single cell analysis to examine MAIT cells in blood, normal and inflamed colonic mucosa. After 9 patients, we have confirmed the decrease in MAIT cell frequency in peripheral blood of UC patients relative to normal blood donors (NBD) but gene expression (GE) profiling was similar for all. Locally, frequency of MAIT cells was increased 6 fold in inflamed colonic mucosa relative to patient matched uninflamed mucosa, while GE profiles revealed differences with peripheral blood MAIT cells and a unique pattern for MAIT cells isolated from inflamed mucosa. The paired TCR sequencing of cells isolated from blood and mucosa is ongoing and will reveal whether different Vb and/or CDRs sequences are correlated to the various activation profiles. Single cell RNA-sequencing will be used to detail the various GE profiles of MAIT cells in all three sites and help us understand the function of these cells in UC lesions. These preliminary results are supportive of a role of MAIT cells in the pathology of UC.