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T cell activation requires two simultaneous signal. The first is binding of the T cell receptor complex (TCR) to a major histocompatibility complex (MHC) molecule carrying a peptide antigen. The second is provided by the binding of the co-stimulatory receptor CD28 to proteins in the surface of the APC, such as B7-2 or B7-1.
Activation of a TCR leads to dephosphorylation of the kinases FYN and LCK by CD45, previously recruited and activated by CD4 and CD8 co-receptors. FYN and LCK phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) on the TCR which then bind the ZAP-70 kinase. Activated ZAP-70 eventually triggers a number of immune responses such as antibody production, activation of phagocytic cells and direct cell killing.