The two-signal model of T-cell activation after 30 years.

The two-signal model of T-cell activation is still valid after 30 years. The recent understanding of the first signal intricacy and its tight relationship with the second signal have thrown decisive light on T-cell activation processes and the complex molecular events that occur on the surface and within the T cell. Furthermore, the recognition of numerous accessory pathways that, in addition to the CD28 and CD40 pathways, operate to manage antigen-presenting cell T cell cooperation in view of lymphocyte activation, disclose the exquisite and numerous regulatory events that compose the second signal.