Figure 1: The anatomy of a cell-fate decision.
In the thymus, immune-cell precursors called thymocytes receive positive selection signals when their T-cell receptors (TCRs) recognize ‘self’ peptides (red circles) bound to molecules of the major histocompatibility complex (MHC) displayed on thymic epithelial cells. This interaction is helped by the CD4 or CD8 proteins. a, The thymocyte recognizes class II MHC, and receives a moderate, prolonged signal. This leads to production of Th-POK, a gene-regulatory protein that in turn controls other genes (including repression of the CD8 gene), causing the cell to adopt a CD4 fate. TCR signalling may also work independently of Th-POK (dashed line) to promote the differentiation or survival of CD4 cells. b, The thymocyte recognizes class I MHC, and receives a weak, transient TCR signal that fails to increase production of Th-POK. TCR-induced events in the absence of Th-POK lead to changes in gene expression (including repression of the CD4 gene), causing the cell to adopt the CD8 fate.
