CD28-mediated co-stimulation: a quantitative support for TCR signalling

The ability of naive T cells to clonally expand and acquire effector functions depends on the strength of signals received by the T-cell receptor (TCR) and by an array of co-stimulatory receptors — the most prominent of which is CD28. In this review, we discuss recent genetic, biochemical and biophysical data that indicate a modified view of the molecular mechanism by which ligation of CD28 amplifies TCR-mediated T-cell activation. These studies indicate that the commonly held notion of a qualitative signalling role of CD28 in T-cell activation should be revised.