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. 2017 May 29;14(9):721–723. doi: 10.1038/cmi.2017.34

Figure 1.

Figure 1

Model of the function of Themis in positive selection. (a) In Themis+/+ DP thymocytes: (1) binding of the TCR on these cells to the self-peptide and MHC complexes causes phosphorylation of ITAM domains on the CD3 co-receptor by Lck; (2) ZAP70 is recruited and phosphorylated; (3) LAT is phosphorylated by ZAP70; (4) LAT recruits GRB2, Themis and SHP-1; and (5) downstream signaling pathways are activated that are sufficient to support positive selection. (b) In thymocytes without a functional Themis: (1) binding of the TCR to the self-peptide and MHC complexes causes phosphorylation of ITAM domains of CD3 by Lck kinase; (2) ZAP70 is recruited and phosphorylated; and (3) ZAP70 and Lck are blocked by the action of SHP-1, which results in the failure of positive selection and death by non-selection.