Title : Insights into
IgA-mediated immune responses from the crystal structures of human
FcalphaRI and its complex with
IgA1-Fc
Abstract :
- Immunoglobulin-alpha ( IgA )-bound antigens induce immune effector responses by activating the IgA-specific receptor FcalphaRI ( CD89 ) on immune cells
- Here we present crystal structures of human FcalphaRI alone and in a complex with the Fc region of IgA1 (Fcalpha) Fcalpha )
- FcalphaRI has two immunoglobulin-like domains that are oriented at approximately right angles to each other
- Fcalpha resembles the Fcs of immunoglobulins IgG and IgE , but has differently located inter chain disulphide bonds and external rather than interdomain N-linked carbohydrates
- Unlike 1:1 FcgammaRIII:Ig G and Fc epsilon RI : IgE complexes, two FcalphaRI molecules bind each Fcalpha dimer , one at each Calpha2-Calpha3 junction
- The FcalphaRI-binding site on IgA1 overlaps the reported polymeric immunoglobulin receptor ( pIgR )-binding site , which might explain why secretory IgA cannot initiate phagocytosis or bind to FcalphaRI-expressing cells in the absence of an integrin co-receptor