E0053

Insights into IgA-mediated Immune Responses from the Crystal Structures of Human FcαRI and its Complex with IgA1-Fc. Andrew B. Herr^1*, Edward R. Ballister¹, and Pamela J. Bjorkman^1,2, ¹Div. of Biology, California Inst. of Technology, Pasadena, CA 91125. ²Howard Hughes Medical Institute.

IgA-bound antigens induce immune effector responses by activating the IgA-specific receptor FcαRI (CD89) on immune cells. Here we present crystal structures of human FcαRI alone and in a complex with the Fc region of IgA1 (Fcα). FcαRI has two immunoglobulin-like domains that are oriented at approximately right angles to each other. Fcα resembles the Fcs of immunoglobulins IgG and IgE, but has differently located interchain disulphide bonds and external rather than interdomain N-linked carbohydrates. Unlike 1:1 FcγRIII:IgG and FcεRI:IgE complexes, two FcαRI molecules bind each Fcα dimer, one at each Cα2–Cα3 junction. The FcαRI-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 FcαRI-expressing cells in the absence of an integrin co-receptor.

*Affiliation starting Fall 2003: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267