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 (1st signal) through the accessory CD3 chains. However, without a 2nd (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) = 1st signal; (2) = 2nd signal.