T cell receptor signalling
T cells are essential white blood cells that control and direct immune responses against invading pathogens and cancer. There are two major types of T cell, referred to as “ab” and “gd”, that both develop in the thymus from a common precursor. The pathways of ab and gd T cell development diverge at a critical thymic checkpoint known as the “b-selection” checkpoint. Here, the decision to adopt one or other fate is governed largely by surface molecules called T cell receptors (TCRs); specifically by the strength with which these receptors transmit a signal to the cell nucleus. This notwithstanding, the mechanisms that underlie this signalling remain unclear. In the journal Science Signaling, an article from the laboratory of Dan Pennington at the Blizard Institute, Barts and The London Medical School, rules out previous models that suggest that either TCR oligomerization or binding of TCR ligands control TCR signalling at the b-selection checkpoint. Instead, the authors propose that T cell precursors at this early checkpoint are particularly sensitive to the amount of TCR on their cell surface. Thus, cells with abundant surface TCR receive stronger TCR signals than favour gd T cell development, while cells with lower surface TCR receive weaker TCR signals that favour ab T cell development. These findings have significant implications for the understanding of how various subsets of T cells develop, and why they adopt certain critical functions that protect the body from life-threatening disease scenarios.