[HTML][HTML] Acquisition of a functional T cell receptor during T lymphocyte development is enforced by HEB and E2A transcription factors

ME Jones, Y Zhuang - Immunity, 2007 - cell.com
ME Jones, Y Zhuang
Immunity, 2007cell.com
The T cell receptor (TCR) is required for positive selection and the subsequent transition
from the CD4+ CD8+ double-positive (DP) to the CD4+ or CD8+ single-positive (SP) stage
of αβ T cell development. The molecular mechanism that maintains DP fate prior to the
acquisition of a functional TCR is not clear. We have shown here that the structurally and
functionally related transcription factors HEB and E2A work together to maintain DP fate and
to control the DP to SP transition. Simultaneous deletion of HEB and E2A in DP thymocytes …
Summary
The T cell receptor (TCR) is required for positive selection and the subsequent transition from the CD4+CD8+ double-positive (DP) to the CD4+ or CD8+ single-positive (SP) stage of αβ T cell development. The molecular mechanism that maintains DP fate prior to the acquisition of a functional TCR is not clear. We have shown here that the structurally and functionally related transcription factors HEB and E2A work together to maintain DP fate and to control the DP to SP transition. Simultaneous deletion of HEB and E2A in DP thymocytes was sufficient for DP to SP transition independent of TCR. Loss of HEB and E2A allowed DP cells to bypass the requirement for TCR-mediated positive selection, downregulate DP-associated genes, and upregulate SP-specific genes. These results identify HEB and E2A as the gatekeepers that maintain cells at the DP stage of development until a functional αβTCR is produced.
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