The Eδ enhancer controls the generation of CD4⁻CD8⁻ αβTCR-expressing T cells that can give rise to different lineages of αβ T cells

It is well established that the pre–T cell receptor for antigen (TCR) is responsible for efficient expansion and differentiation of thymocytes with productive TCRβ rearrangements. However, Ptcra- as well as Tcra-targeting experiments have suggested that the early expression of Tcra in CD4⁻CD8⁻ cells can partially rescue the development of αβ CD4⁺CD8⁺ cells in Ptcra-deficient mice. In this study, we show that the TCR Eδ but not Eα enhancer function is required for the cell surface expression of αβTCR on immature CD4⁻CD8⁻ T cell precursors, which play a crucial role in promoting αβ T cell development in the absence of pre-TCR. Thus, αβTCR expression by CD4⁻CD8⁻ thymocytes not only represents a transgenic artifact but occurs under physiological conditions.