Two-Signal Model for T-Cell Activation

The alpha (α) and beta (β) chains of the T-cell receptor (TCR) bind to antigen (Ag)–major histocompatibility complex (MHC) on an antigen-presenting cell (APC), and CD4 or CD8 interacts with the MHC. Both actions stimulate the T cell (first signal) through the accessory CD3 chains. However, without a second (coactivation) signal, the T cell is anergic or tolerant.

The TCR is structurally homologous to the B-cell receptor; the α and β (or gamma [γ] and delta [δ]) chains have constant (C) and variable (V) regions. (1) = first signal; (2) = second signal.