TCR Signaling Circuits in αβ/γδ T Lineage Choice

Excerpt

Both of the major T lineages, αβ and γδ, arise from a common CD4^-CD8^- double negative (DN) progenitor in the thymus. Although the molecular processes responsible for specification of these alternate cell fates remain incompletely understood, recent efforts have begun to shed light on the influence of the T cell antigen receptor (TCR) complex and the molecular effectors it employs. This chapter will summarize our current understanding of how distinct TCR signals drive an uncommitted progenitor to adopt the alternate αβ or γδ lineages, as well as how those TCR signals influence γδ effector fates. Particular attention is paid to the emerging role of the extracellular signal-regulated kinase (ERK)-early growth response (Egr)-inhibitor of DNA binding 3 (Id3) pathway, and how its influence on E protein function impacts fate specification. Outstanding questions and the advances in technology that can be used to address them will be highlighted.