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Question: The molecule, ARUS, plays a role in regulation of TCR signalling and the gene (Arus) has been linked to autoimmune disease risk. A recent study showed deletion of Arus in mice (i.e., the mice cannot produce ARUS) led to suppression of TCR signalling in DP thymocytes, but not in single positive (SP) thymocytes. In other words, without ARUS when the TCR on the DP thymocyte binds MHC-peptide on the APC, a weaker signal is generated than when ARUS is present. The presence of ARUS does not affect the affinity of TCR for its target MHC-peptide, just the signal strength generated. Based on what we have learned of thymocyte/T-cell development, identify the important events occurring during the DP thymocyte stage and describe how you would expect the outcomes of these events to change if TCR signalling is significantly decreased. Why might the changes you describe impact autoimmune disease risk? Note, for outcomes focus on cell-level consequences (e.g., "more cells would die", "more non-productive cells would live", "cells would revert to the DN stage", etc.). Further note, you are being asked about T-cell/thymocyte development, you have not been asked to comment about activation of mature T-cells in these mice.
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