TCRA Gene Rearrangement in Immature Thymocytes in Absence of CD3, Pre-TCR, and TCR Signaling

Abstract

During thymocyte differentiation, TCRA genes are massively rearranged only after productively rearranged TCRB genes are expressed in association with pTα and CD3 complex molecules within a pre-TCR. Signaling from the pre-TCR via the CD3 complex is thought to be required to promote TCRA gene accessibility and recombination. However, αβ+ thymocytes do develop in pTα-deficient mice, showing that TCRα-chain genes are rearranged, either in CD4−CD8− or CD4+CD8+ thymocytes, in the absence of pre-TCR expression. In this study, we analyzed the TCRA gene recombination status of early immature thymocytes in mutant mice with arrested thymocyte development, deficient for either CD3 or pTα and γc expression. ADV genes belonging to different families were found rearranged to multiple AJ segments in both cases. Thus, TCRA gene rearrangement is independent of CD3 and γc signaling. However, CD3 expression was found to play a role in transcription of rearranged TCRα-chain genes in CD4−CD8− thymocytes. Taken together, these results provide new insights into the molecular control of early T cell differentiation.