Summary
Antibodies constitute an integral arm of the adaptive immune system that, in its fight against viruses, can occasionally perform as a double-edged sword. Antibodies are Y-shaped molecules. Historically, research on humoral responses to viral infection have mostly focused on the V end of the Y: the antigen-binding regions, or Fab, which bind and neutralize viral infections. Conversely, the tail of the Y (also called the fragment crystallizable, or Fc, domain) possesses numerous functional properties—namely induction of antibody-dependent complement deposition, cellular phagocytosis and cellular cytotoxicity (1)—but is relatively understudied. On page 1102 of this issue, Bournazos et al. (2) and another recent study by Larsen et al. (3) demonstrate that modifying the Fc domain with chains of sugar molecules (glycosylation) can trigger cellular immune functions that can either protect against or worsen viral diseases, such as dengue and COVID-19.