Costimulatory molecule programmed death-1 in the cytotoxic response during chronic hepatitis C

Figure 1 Programmed death-1 (PD-1) structure and interactions. Interaction between the PD-1 molecule expressed on T cells and its ligand PD-L1 expressed on antigen-presenting cells leads to immunoreceptor tyrosine-based switch motif (ITSM) motif phosphorylation in its cytoplasmic tyrosines which are recognized by src homology 2 domain-containing tyrosine phosphatase 2 (SHP-2). All of these interactions cause T cell anergy due to T cell receptor (TCR)-dependent MAP Kinase-pathway signalling inhibition which avoids interleukin (IL)-2 gene transduction. PD-1 expression is induced by TCR activation but could also be favoured by HCV-core protein through interaction with gC1qR. PD-L1 is up-regulated on antigen presenting cells by the effect of γ-interferon produced during HCV infection by activated lymphocytes.