Immune mechanisms of vaccine induced protection against chronic hepatitis C virus infection in chimpanzees

Figure 2 Summary of immune responses in hepatitis C virus immunized chimpanzees. Antigen presenting cells (DCs or Kupffer cells in the liver) present HCV peptides in the context of major histocompatibility complex class II molecules to the T-cell receptor (TCR) on CD4 T-cells. CD4 cells may activate B-cells. Antibodies produced may be neutralizing and bind to circulating HCV particles and prevent the infection of hepatocytes. Or the antibodies may be non-neutralizing antibodies and potentially play a role in ADCC. CD4-helper T-cells can also stimulate cytolytic T-cells. CD8 T-cells may be directly responsible for lysis when they produce degranulation molecules like granzymes or perforin after the recognition of a peptide on the surface of an HCV infected hepatocyte. Or via indirect lysis, mediated by the secretion of cytokines. CD8 T-cells affected by Tregs and exhausted CD8 T-cells are functionally impaired and are incapable of lysing HCV infected hepatocytes. HCV: Hepatitis C virus; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4; IFN: Interferon; TNFα: Tumor necrosis factor alpha; ADCC: Antibody dependent cellular cytotoxicity; DC: Dentritic cell; PD-1: Programmed cell death protein 1; TIM-3: T cell immunoglobulin and mucin protein 3; LAG-3: Lymphocyte-activation gene 3.