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Haks Marielle C , Lefebvre Juliette M , Lauritsen Jens Peter H , Carleton Michael , Rhodes Michele , Miyazaki Toru , Kappes Dietmar J , Wiest David L
Attenuation of gdTCR signaling efficiently diverts thymocytes to the ab lineage
Immunity. 2005 ;22(5) :595-606
PMID: AN 2005:477936   
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The role of the T cell antigen receptor complex (TCR) in ab/gd lineage commitment remains controversial, in particular whether different TCR isoforms intrinsically favor adoption of a certain lineage. Here, we demonstrate that impairing the signaling capacity of a gdTCR complex enables it to efficiently direct thymocytes to the ab lineage. In the presence of a ligand, a transgenic gdTCR mediates almost exclusive adoption of the gd lineage, while in the absence of ligand, the same gdTCR promotes ab lineage development with efficiency comparable to the pre-TCR. Importantly, attenuating gdTCR signaling through Lck deficiency causes reduced ERK1/2 activation and Egr expression and diverts thymocytes to the ab lineage even in the presence of ligand. Conversely, ectopic Egr overexpression favors gd T cell development. Our data support a model whereby gd vs. ab lineage commitment is controlled by TCR signal strength, which depends critically on the ERK MAPK-Egr pathway. [on SciFinder (R)]
CAN 143:25021 15-10 Immunochemistry Division of Basic Sciences Immunobiology Working Group,Fox Chase Cancer Center,Philadelphia,PA,USA. Journal 1074-7613 written in English. 137632-07-6 (Erk 1 kinase); 137632-08-7 (Erk 2 kinase); 142243-02-5 Role: BSU (Biological study, unclassified), BIOL (Biological study) (attenuation of gdTCR signaling efficiently diverts thymocytes to the ab lineage)