FIGURE 23-33 Signals involved in T-cell activation and its termination. The two-signal model of T-cell activation involves recognition of an MHC-peptide complex by the T-cell receptor, which constitutes signal 1 (step 1), along with recognition of co-stimulatory molecules (CD80, CD86) on the surface of an antigen-presenting cell, which constitutes signal 2 (step 2). If co-stimulation is not provided, the newly engaged T cell becomes unresponsive (anergic). The provision of both signal 1 via the T-cell receptor and signal 2 via engagement of CD80 and CD86 by CD28 allows full activation. Full activation, in turn, leads to increased expression of CTLA4 (step 3). After moving to the T-cell surface, CTLA4 binds CD80 and CD86, leading to inhibition of the T-cell response (step 4). Because the affinity of CTLA4 for CD80 and CD86 is greater than that of CD28, T-cell activation is eventually terminated.