Signals elicited by binding of the T-cell antigen receptor and the CD4/CD8 
co-receptor to major histocompatibility complex (MHC) molecules control the 
generation of CD4+ (helper) or CD8+ (cytotoxic) T cells from thymic precursors 
that initially express both co-receptor proteins. These precursors have unique, 
clonally distributed T-cell receptors with unpredictable specificity for the 
self-MHC molecules involved in this differentiation process. However, the mature 
T cells that emerge express only the CD4 (MHC class II-binding) or CD8 (MHC 
class I-binding) co-receptor that complements the MHC class-specificity of the 
T-cell receptor. How this matching of co-receptor-defined lineage and 
T-cell-receptor specificity is achieved remains unknown, as does whether 
signalling by the T-cell receptors, co-receptors and/or general cell-fate 
regulators such as Notch-1 contributes to initial lineage choice, to subsequent 
differentiation processes or to both. Here we show that the CD4 versus CD8 
lineage fate of immature thymocytes is controlled by the co-receptor-influenced 
duration of initial T-cell receptor-dependent signalling. Notch-1 does not 
appear to be essential for this fate determination, but it is selectively 
required for CD8+ T-cell maturation after commitment directed by T-cell 
receptors. This indicates that the signals constraining CD4 versus CD8 lineage 
decisions are distinct from those that support subsequent differentiation events 
such as silencing of co-receptor loci.