FcαRI binding at the IgA1 C2-C3 interface induces long-range conformational changes that are transmitted to the hinge region.

IgA effector functions include proinflammatory immune responses triggered upon clustering of the IgA-specific receptor, FcαRI, by IgA immune complexes. FcαRI binds to the IgA1-Fc domain (Fcα) at the C2-C3 junction and, except for C2 L257 and L258, all side-chain contacts are contributed by the C3 domain. In this study, we used experimental and computational approaches to elucidate energetic and conformational aspects of FcαRI binding to IgA.

IgG1 protects against renal disease in a mouse model of cryoglobulinaemia.

Immunoglobulins protect against disease to a considerable extent by activating complement and stimulatory immunoglobulin crystallizable fragment receptors (Ig FcRs), and aggregating microbial pathogens. Yet IgG1, the predominant murine serum Ig isotype, cannot activate complement by the classical pathway, binds more avidly to an inhibitory than to stimulatory FcRs, and has limited ability to aggregate pathogens. In these regards, it resembles human IgG4 (ref.