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TitleMolecular parameters governing antibody FcγR signaling and effector functions in the context of HIV envelope.
Journal, issue, pagesCell Rep, Vol. 44, Issue 4, Page 115331, Year 2025
Publish dateMar 28, 2025
AuthorsMichael 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 /
PubMed AbstractAntibody 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.
External linksCell Rep / PubMed:40158219
MethodsEM (single particle)
Resolution25.0 - 34.0 Å
Structure data

EMDB-42907: sRT-V2t NFL trimer in complex with 12CA5 Fab and RM20A3 Fab
Method: EM (single particle) / Resolution: 32.0 Å

EMDB-42908: sRT-V1 NFL trimer in complex with 12CA5 Fab
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-42909: sRT-V3 NFL trimer in complex with 12CA5 Fab and RM20A3 Fab
Method: EM (single particle) / Resolution: 34.0 Å

EMDB-42910: sRT-Bttm NFL trimer in complex with 12CA5 Fab
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-42912: sRT-C3V5 NFL trimer in complex with 12CA5 Fab and RM20A3 Fab
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-42913: sRT-V4 NFL trimer in complex with 12CA5 Fab and RM20A3 Fab
Method: EM (single particle) / Resolution: 33.0 Å

Source
  • Human immunodeficiency virus 1

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