Figure 3.

Enhancement of antigen-clearance by acid-switching.

A. pH-independent binding. Antibodies that bind to antigen with similar affinity in the pH range 6.0–7.4 enter cells by fluid-phase pinocytosis in small tubulovesicular TCs that fuse with early (sorting) endosomes in which binding to FcRn can occur, followed by recycling of the IgG:antigen complex and exocytic release at the plasma membrane. This results in the buffering effect that prolongs the half-life of the targeted antigen.

B. Acid-switched binding. By contrast, pH-dependent or acid-switched antibodies have substantially higher affinity for antigen at near neutral pH relative to acidic, endosomal pH. Following internalization into cells by fluid-phase pinocytosis in small tubulovesicular TCs, the complexes enter acidic sorting endosomes in which antigen dissociates from antibody and enters the lysosomal pathway. The FcRn-bound antibody is recycled and exocytosed. This results in increased clearance of antigen combined with recycling of antibody for re-use.