National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
UM1 AI144462
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI136621-05
米国
引用
ジャーナル: Cell Rep / 年: 2025 タイトル: Molecular parameters governing antibody FcγR signaling and effector functions in the context of HIV envelope. 著者: Michael V Bick / Eduard Puig / David Beauparlant / Rebecca Nedellec / Iszac Burton / Keihvan Ardaghi / Thea R Zalunardo / Raiza Bastidas / Xuduo Li / Javier Guenaga / Wen-Hsin Lee / Richard ...著者: Michael V Bick / Eduard Puig / David Beauparlant / Rebecca Nedellec / Iszac Burton / Keihvan Ardaghi / Thea R Zalunardo / Raiza Bastidas / Xuduo Li / Javier Guenaga / Wen-Hsin Lee / Richard Wyatt / Wenwen Zhu / Max Crispin / Gabriel Ozorowski / Andrew B Ward / Dennis R Burton / Lars Hangartner / 要旨: 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 ...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 investigated, were of no substantial impact. These findings are of importance for informing the development of vaccination strategies against HIV-1 and, possibly, other viral pathogens.