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HEB and E2A enforce TCR checkpoint in T lymphocyte development
Author(s) -
Zhuang Yuan,
Jones Mary Elizaberth
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.661.6
Subject(s) - t cell receptor , cd8 , biology , transcription factor , gene , microbiology and biotechnology , transition (genetics) , t cell , t lymphocyte , transcription (linguistics) , genetics , antigen , immune system , linguistics , philosophy
The T cell receptor (TCR) is required for positive selection and the subsequent transition from CD4 + CD8 + double positive (DP) to CD4 + or CD8 + single positive (SP) stage of αβ T cell development. The molecular mechanism which maintains DP fate prior to the acquisition of a functional TCR is not clear. We will present genetic data to show 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. We demonstrate that simultaneous deletion of HEB and E2A in DP thymocytes is sufficient for DP to SP transition independent of TCR. Loss of HEB and E2A allows DP cells to bypass the requirement for TCR‐mediated positive selection, down‐regulate DP associated genes, and up‐regulate SP specific genes. Our work identifies HEB and E2A as the gatekeepers that maintain cells at the DP stage of development until a functional αβ TCR is produced.