Unknown

Dataset Information

0

General mechanism for modulating immunoglobulin effector function.


ABSTRACT: Immunoglobulins recognize and clear microbial pathogens and toxins through the coupling of variable region specificity to Fc-triggered cellular activation. These proinflammatory activities are regulated, thus avoiding the pathogenic sequelae of uncontrolled inflammation by modulating the composition of the Fc-linked glycan. Upon sialylation, the affinities for Fc? receptors are reduced, whereas those for alternative cellular receptors, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)/CD23, are increased. We demonstrate that sialylation induces significant structural alterations in the C?2 domain and propose a model that explains the observed changes in ligand specificity and biological activity. By analogy to related complexes formed by IgE and its evolutionarily related Fc receptors, we conclude that this mechanism is general for the modulation of antibody-triggered immune responses, characterized by a shift between an "open" activating conformation and a "closed" anti-inflammatory state of antibody Fc fragments. This common mechanism has been targeted by pathogens to avoid host defense and offers targets for therapeutic intervention in allergic and autoimmune disorders.

SUBMITTER: Sondermann P 

PROVIDER: S-EPMC3683708 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

General mechanism for modulating immunoglobulin effector function.

Sondermann Peter P   Pincetic Andrew A   Maamary Jad J   Lammens Katja K   Ravetch Jeffrey V JV  

Proceedings of the National Academy of Sciences of the United States of America 20130522 24


Immunoglobulins recognize and clear microbial pathogens and toxins through the coupling of variable region specificity to Fc-triggered cellular activation. These proinflammatory activities are regulated, thus avoiding the pathogenic sequelae of uncontrolled inflammation by modulating the composition of the Fc-linked glycan. Upon sialylation, the affinities for Fcγ receptors are reduced, whereas those for alternative cellular receptors, such as dendritic cell-specific intercellular adhesion molec  ...[more]

Similar Datasets

| S-EPMC8607236 | biostudies-literature
| S-EPMC4347774 | biostudies-literature
| S-EPMC8571096 | biostudies-literature
| S-EPMC3412026 | biostudies-literature
2024-08-10 | GSE264061 | GEO
| S-EPMC1895796 | biostudies-literature
| S-EPMC4553773 | biostudies-literature
| S-EPMC3226764 | biostudies-literature
| S-EPMC2043195 | biostudies-literature
| S-EPMC5649276 | biostudies-literature