Document Detail

Acquisition of a functional T cell receptor during T lymphocyte development is enforced by HEB and E2A transcription factors.
MedLine Citation:
PMID:  18093538     Owner:  NLM     Status:  MEDLINE    
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 alphabeta 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 alphabetaTCR is produced.
Mary Elizabeth Jones; Yuan Zhuang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Immunity     Volume:  27     ISSN:  1074-7613     ISO Abbreviation:  Immunity     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-12-20     Completed Date:  2008-02-05     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  9432918     Medline TA:  Immunity     Country:  United States    
Other Details:
Languages:  eng     Pagination:  860-70     Citation Subset:  IM    
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MeSH Terms
Basic Helix-Loop-Helix Transcription Factors / physiology*
CD8-Positive T-Lymphocytes / physiology
Receptors, Antigen, T-Cell / physiology*
T-Lymphocytes / physiology*
Grant Support
R01 CA072433/CA/NCI NIH HHS; R01 CA072433-10/CA/NCI NIH HHS; R01 GM059638/GM/NIGMS NIH HHS; R01 GM059638-08/GM/NIGMS NIH HHS
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Receptors, Antigen, T-Cell; 0/Tcf12 protein, mouse; 0/Tcf3 protein, mouse

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