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Review

Nature Reviews Immunology 3, 939–951 (1 December 2003) | doi:10.1038/nri1248

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

Oreste Acuto & Fr|[eacute]|d|[eacute]|rique Michel

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.