The role of ephrinB1 and ephrinB2 in controling gamma-delta T cell development

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The applicant is a pioneer in Eph/ephrin research. This research has been a major program (with funding from other sources) in his lab since 2000. The short-term objectives described hereafter to be carried out in the next 5 years are a part of a long-term program, which will be in full swing for the next 10 years and more, and the objectives of which are to elucidate the roles of Ephs/ephins in the immune system and cardiovascular system. Three to six Ph.D. students will be trained in the next 10 years using the program as a vehicle. This long-term program will be a dedicated NSERC program. In our immune system, there are two types of cells called alpha/beta T cells and gamma/delta T cells, and both of them are developed in the thymus and they have common ancestors. What determines the decision of the ancestors to become alpha/beta T cells and gamma/delta T cells is not fully understood. We found that two molecules called can influence the decision making of the ancestors. In this project, we will investigate the underlying mechanisms of this finding. We have two non-mutually exclusive hypotheses: 1) EFNB1/B2 interact with or modulate molecules known to regulate decision-making of the ancestors; 2) EFNB1/B2 are modulators of the decision making in their own right. The specific aims of this project are as follows: 1. To investigate whether EFNB1/B2 interact physically with and affect the function of known molecules that control the ancestor decision making. 2. To evaluate whetherEFNB1/B2 promote the survival and growth of gamma/delta T cells. 3. To investigate how EFNB1/B2 trigger a cascade of other molecules inside the ancestor cells for their decision making. Significance. This study will generate new knowledge in gamma/delta T cell fate determination.