T-cell receptor (TCR) signalling
T-cell receptor (TCR) signalling — full pathway. Antigen recognition by the TCR/CD3 complex (with the CD4/CD8 co-receptor and its kinase Lck) and CD28 co-stimulation launches a proximal cascade — Lck/Fyn → ZAP-70 → LAT/SLP-76 — that fans into five effector arms: the actin/cytoskeleton synapse, Ca2+/calcineurin/NFAT, PKCθ/CBM/NF-κB, Ras/MAPK/AP-1 and PI3K/AKT/mTOR — balanced by inhibitory receptors and phosphatases (CTLA-4, PD-1, CD45, SHP-1/2, PTEN, Cbl-b, DGKα). Click any protein for the matching Assay Genie In Vivo functional-grade antibody or ELISA kit.
Initiation. Peptide-MHC engages the TCR/CD3 complex while the CD4 or CD8 co-receptor delivers Lck; CD45 primes Lck and Csk restrains it. Lck (and Fyn) phosphorylate the CD3 ITAMs, recruiting ZAP-70, which builds the LAT/SLP-76/Gads signalosome and activates Itk and PLCγ1.
Five arms. PLCγ1 splits PIP2 into DAG and IP3. IP3→Ca2+/calmodulin activates calcineurin → NFAT; DAG drives PKCθ → CARMA1-Bcl10-MALT1 → IKK → IκB → NF-κB and RasGRP/Grb2-SOS → Ras → Raf → MEK → ERK → Elk-1 / c-Fos (with JNK → c-Jun) to build AP-1. Vav1 → Rac1 → WASP → cofilin remodels actin for the immune synapse. CD28 fires PI3K → PDK1 → AKT → mTOR, inhibiting GSK-3β and FOXO1 for growth and survival.
Brakes. CTLA-4 outcompetes CD28; PD-1 recruits SHP-2; SHP-1 and PTEN dephosphorylate the cascade; Cbl-b and DGKα raise the threshold and enforce anergy when co-stimulation is absent. The transcription factors NFAT, NF-κB, AP-1, Elk-1, c-Myc and FOXO1 then set proliferation, IL-2 & effector cytokines, survival and synapse formation. Assay Genie In Vivo functional-grade antibodies target the surface layer (anti-CD3/CD4/CD8/CD28, anti-CTLA-4, anti-PD-1) and neutralise IL-2; the intracellular network is covered by ELISA kits and antibodies. For research use only; not for diagnostic or therapeutic procedures. Mouse targets shown where available.
Every one of the ~50 protein nodes links to a product: In Vivo antibodies for the surface receptors, checkpoints and IL-2; the intracellular kinases, adaptors, GTPases, phosphatases and transcription factors open the matching ELISA kit or antibody.