User:Kinkreet/Immunology/T cell Activation

T cell activation requires two signals: the binding of the T cell receptor (TCR) to processed antigen presented on MHC molecules (Class I for cytotoxic T cells, and Class II for helper T cells), and a co-stimulatory signal.

TCR/MHC
TCR binds to processed antigen presented on MHC molecules. CD4/8 ols acts an the T cels co-receptors and bind to a conserved region on the MHC molecule itself and activates intracellular Lck using protein phosphatase CD45 to dephosphorylate Lck. T killer cells display CD8, which consists of an α and a β domain, and can bind to MHC Class I; T helper cells display CD4, which have 4 D domains and can bind to MHC Class II. Activated Lck phosphorylates multiple two-tyrosine residues ITAM motifs on TCRζ and CD3, which then acts as a docking site for the SH2 domains of other protein tyrosine kinases (PTKs) such as Zeta-chain-associated protein kinase 70 (ZAP-70). The docked ZAP-70 is phosphorylated by Lck or Fyn, which activates it to phosphrylate PTKs downstream. ZAP-70 is a PTK of the Syk family, and it catalyse the activation (by phosphorylation) of phospholipase C-γ1 (PLC-γ1). The activated phospholipase Cγ hydrolyses phosphoinositides, which produce two different products, each inducing transcription using separate pathways - diacylglyceride (DAG) activates protein kinase C (PKC); and IP3 increases the concentration of cytosolic Ca2+ concentration.

Apart from the cell-to-cell costimulation, soluble signals also need to be received, not so much for activation, but for differentiation; i.e. the TH cell chooses which pathway to take depending on the cytokines it receives.

Co-stimulatory
The activated T cell release IL-2, which works in an autocrine and paracrine manner, to induces proliferation and differentiation, so that when it encounters that specific antigen, it will no longer require costimulation to respond.