Exit of the Pre-TCR from the ER/cis-Golgi Is Necessary for Signaling Differentiation, Proliferation, and Allelic Exclusion in Immature Thymocytes

AbstractA major issue is whether surface expression of the pre-TCR is necessary for signaling the development of immature thymocytes. To address this question, we generated transgenic mice expressing a TCRβ chain that had a strong endoplasmic reticulum (ER) retrieval signal (TCRβER) and that was expressed intracellularly but failed to reach the cell surface. In TCRβER transgenic mice, there was a failure of allelic exclusion. Also, the transgene failed to rescue the developmental defects observed in TCRβ-null mice. In contrast, TCRβ transgenes with a mutant ER retrieval sequence or lacking this sequence signaled efficient allelic exclusion and suppressed the TCRβ−/− defect. These data show that exit of the pre-TCR from the ER/cis-Golgi is required for progression through the double-negative thymocyte checkpoint