Figure 1. Receptors for antigen.
a, T cell receptor (TCR). Physiological antigen recognition is mediated by the TCR–CD3 complex, which comprises six independent gene products: the TCR α and β chains, which together bind to HLA–peptide complexes, and the CD3γ, δ, ε and ζ chains, which initiate T cell activation. b, Chimaeric antigen receptor (CAR). A prototypic second-generation CAR comprises three canonical domains for binding to antigen (unrestricted by HLA), T cell activation (commonly via the CD3ζ cytoplasmic domain) and co-stimulation (via the CD28 cytoplasmic domain in this example). The hinge and transmembrane domain also contribute to overall CAR function. c, Synthetic receptors in the extended CAR family: chimaeric co-stimulatory receptors (CCRs) provide co-stimulation in response to antigen or alternate ligands; chimaeric cytokine receptors (CyCRs) bind to one cytokine but transduce the signal of another; antigen-specific inhibitory receptors (iCARs) inhibit T cell activation in response to an antigen; synthetic Notch (synNotch) receptors induce CAR expression after antigen recognition by a chimaeric Notch receptor. The scissors indicate a cleavage site that releases a transcription factor (TF).