Molecular parameters governing antibody FcγR signaling and effector functions in the context of HIV envelope.

ABSTRACT: Antibody effector functions contribute to the immune response to pathogens and can influence the efficacy of antibodies as therapeutics. To date, however, there is limited information on the molecular parameters that govern fragment crystallizable (Fc) effector functions. In this study, using AI-assisted protein design, the influences of binding kinetics, epitope location, and stoichiometry of binding on cellular Fc effector functions were investigated using engineered HIV-1 envelope as a model antigen. For this antigen, stoichiometry of binding was found to be the primary molecular determinant of FcγRIIIa signaling, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis, while epitope location and antibodybinding kinetics, at least in the ranges investigate

SUBMITTER: Bick MV 

PROVIDER: S-EPMC12815480 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature