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Date of Award
Immunology and Microbiology
Human Mucosal Associated Invariant T (MAIT) cells are innate-like T cells that express the TCRα chain, Vα7.2 and are restricted by the evolutionarily conserved major histocompatibility complex (MHC)-Related Protein 1, MR1. They are involved in protective immunity against bacteria and yeast infections, and play potential roles in cancer and autoimmune disease development. With further study into their diverse functions, MAIT cells have been suggested to be a heterogeneous population despite their MR1 restricted TCR repertoire. Recently, a new technology called single-cell RNA sequencing (scRNA-seq) has been developed that enables the profiling of cellular transcriptomes at single cell resolution and offers an unbiased approach to studying immune cell heterogeneity. Here, we split 23,200 peripheral blood MAIT cells from eight patients into two groups: one stimulated with PMA/ionomycin and the other left untreated in the steady state, and performed single-cell RNA-sequencing to provide an unbiased survey of their heterogeneity. Our analysis reveals several novel subsets that redefine MAIT cells including a B4GALT1+ subset with potential involvement in mucosa cancers and a previously defined KLRD1+ subset with cytotoxic transcriptional machinery. Additionally, we reveal a potential population in the exhausted state as well as a novel rare subset potentially capable of sensing and responding to short chain fatty acids from commensal bacteria. We further investigated the transcriptomic variations across activating conditions with an integrated analysis of all data sets thus providing greater insight into the transcriptional machinery of MAIT cells. Overall, we provide an unbiased analysis of human peripheral blood MAIT cells and putative cluster-specific biomarkers for potential MAIT cell-based immunotherapies in infectious, malignant, and autoimmune diseases.
Cvetkovski, Steven, "Single Cell Rna Sequencing Reveals Novel Subpopulations And Biomarkers Of Mucosal Associated Invariant T (mait) Cells" (2019). Wayne State University Theses. 699.