Attenuation of γδTCR signaling efficiently diverts thymocytes to the αβ lineage

Abstract

The role of the T cell antigen receptor complex (TCR) in αβ/γδ 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 γδTCR complex enables it to efficiently direct thymocytes to the αβ lineage. In the presence of a ligand, a transgenic γδTCR mediates almost exclusive adoption of the γδ lineage, while in the absence of ligand, the same γδTCR promotes αβ lineage development with efficiency comparable to the pre-TCR. Importantly, attenuating γδTCR signaling through Lck deficiency causes reduced ERK1/2 activation and Egr expression and diverts thymocytes to the αβ lineage even in the presence of ligand. Conversely, ectopic Egr overexpression favors γδ T cell development. Our data support a model whereby γδ versus αβ lineage commitment is controlled by TCR signal strength, which depends critically on the ERK MAPK-Egr pathway. Copyright ©2005 by Elsevier Inc.