Role of RasGRP1 in regulating lymphocyte development and function

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T cells, an important component of the adaptive immune system, are derived from stem cells that undergo differentiation in an organ called the thymus. T cells can be broadly separated into two distinct lineages, αβ T cells and γδ T cells, based upon the class of T cell receptor (TCR) they express. These lineages arise from a bi-potent progenitor. While much is known regarding the signaling pathways required for development of αβ T cells, the role of these same signaling pathways in γδ T cell development is unclear. Furthermore, unlike most αβ T cells, γδ T cells possess the ability to rapidly produce cytokines. Signaling through the Ras pathway has been demonstrated to regulate the development of γδ-thymocytes. However, it is unclear which family of Ras activators, the Ras guanyl nucleotide releasing protein (RasGRP) or the Son of Sevenless (Sos) family is required for Ras activation in the context of gd-thymocyte development. Published data from us and others and our preliminary data suggest that RasGRP1 deficiency plays a critical role in γδ thymocyte development.