Heterogeneity of immune control in chronic hepatitis B virus infection: Clinical implications on immunity with interferon-α treatment and retreatment

Figure 2 Mechanism of immune escape in antigen-presenting cell/hepatitis B virus special T-cell. Hepatitis B virus (HBV)-infected hepatocytes produce various HBV antigens that are swallowed and digested by antigen-presenting cells (APCs), producing HBV peptide/human leukocyte antigen (HLA) complexes. Antigen processing escape mutants, down-regulating HLA expression and mutation of HLA binding residues may appear in APCs. The HBV peptide/HLA complexes are transferred to the surface of APC and make contact with T-cell receptor (TCR) on the surface of CD8⁺ T-cells. Masking HLA/TCT binding residues with N-linked glycosylation and mutation of TCR binding residues influences TCR affinity/avidity, leading to CD8⁺ T-cell stimulation or inhibition. The square icon displays: (1) Increase in viral antigen; (2) Antigen processing escape mutants; (3) Down-regulation of HLA expression; (4) Mutation of HLA binding residues; (5) Masking of HLA/TCT binging residues with N-linked glycosylation; (6) Mutation of TCR binding residues; (7) Stimulation induced by cytokine production and cytolytic activity; and (8) Inhibition caused by exhaustion, anergy and tolerance. HBV: Hepatitis B virus; TCR: T-cell receptor; HLA: Human leukocyte antigen.