Human immune repertoire in hepatitis B virus infection

Figure 1 T-cell receptor and B-cell receptor structure and signaling pathways. T-cell receptor and B-cell receptor complexes include both variable antigen-recognition proteins and invariant signaling proteins. Phosphorylation of the ITAMs in CD3 ε, γ, δ, and the ζ chain enables them to bind the cytosolic tyrosine kinase ZAP-70, which in turn recruits and activates PLC-γ. Activated PLC-γ cleaves PIP₂ to yield DAG and IP₃. IP₃ increases intracellular Ca²⁺ concentration, activating calcineurin, a phosphatase that then activates an NFAT transcription factor. DAG recruits PKC to activate CARMA, which leads to activation of NF-κB and recruits RasGRP, which activates AP-1. These three important signaling pathways activate transcription factors in the nucleus, including NF-κB, NFAT, and AP-1, which result in cell differentiation, proliferation, and immune response. AP-1: Activator protein-1; CARMA: Caspase recruitment domain family, member 14 protein; DAG: Diacylglycerol; IP₃: Inositol trisphosphate; ITAM: Immunoreceptor tyrosine-based activation motif; NFAT: Nuclear factor of activated T cells; NF-κB: Nuclear factor kappa B; PIP₂: Phosphatidylinositol bisphosphate; PKC: Protein kinase C; PLC-γ: Phospholipase C-γ; RasGRP: RAS guanyl releasing protein; Syk: Spleen-associated tyrosine kinase; ZAP-70: Zeta chain of T-cell receptor-associated protein kinase 70.