Early expression of mature αβ TCR in CD4^-CD8^- T cell progenitors enables MHC to drive development of T-ALL bearing NOTCH mutations.

ABSTRACT: During normal T cell development in mouse and human, a low-frequency population of immature CD4^-CD8^- double-negative (DN) thymocytes expresses early, mature αβ T cell antigen receptor (TCR). We report that these early αβ TCR+ DN (EADN) cells are DN3b-DN4 stage and require CD3δ but not major histocompatibility complex (MHC) for their generation/detection. When MHC - is present, however, EADN cells can respond to it, displaying a degree of coreceptor-independent MHC reactivity not typical of mature, conventional αβ T cells. We found these data to be connected with observations that EADN cells were susceptible to T cell acute lymphoblastic leukemia (T-ALL) transformation in both humans and mice. Using the OT-1 TCR transgenic system to model EADN-stage αβ TCR expression,

SUBMITTER: Laffey KG 

PROVIDER: S-EPMC9271211 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature