Unconventional T cell development in the human postnatal thymus 2829

Abstract Description Unconventional T cells are a subset of T cells that recognize a range of non-peptide antigens, such as lipids, vitamin B metabolites, and phosphoantigens. These antigens are presented by non-classical antigen-presenting molecules, including CD1, MHC-related 1 (MR1), and butyrophilin molecules. Unconventional T cells include CD1-restricted T cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells. Unconventional T cells can rapidly produce large amounts of cytokines upon activation and are suggested as being crucial in the interface of innate and adaptive immunity. These cells are implicated in various human diseases, including cancer and autoimmune disorders, with alterations in both their frequency and function noted. Therefore, understanding their developmental pathways is critical for uncovering potential mechanisms behind these diseases. This knowledge could inform the development of targeted therapies to modulate unconventional T cells and their responses for clinical benefit. Using a combination of high-dimensional flow cytometry, transcriptomic and functional analysis, and precursor-product experiments, we have mapped the postnatal thymic development pathways of MAIT, Vγ9Vδ2, and NKT cells. This revealed shared and unique features of their development, providing insights into their unique biology. This new understanding could pave the way for novel therapeutic strategies that leverage the unique properties of unconventional T cells in disease contexts. Funding Sources NHMRC ideas grant Topic Categories Hematopoiesis and Immune System Development (HEM)