Fc alpha/mu receptor (Fc alpha/mu R), a novel Fc receptor for IgA and IgM, is a type I transmembrane protein with an immunoglobulin (Ig)-like domain in the extracellular portion. Although IgA and IgM bind to Fc alpha/mu R, the molecular and structural characteristics of the ligand-receptor interactions have been undetermined. Here, we developed twelve monoclonal antibodies (mAbs) against murine Fc alpha/mu R by. P se blocking immunizing mice deficient in Fc alpha/mu R gene. Eight mAbs totally or partially blocked IgA and IgM bindings to Fc alpha/mu R. The mAbs bound to a peptide derived from the Ig-like domain of murine Fc alpha/mu R, which is conserved not only in human and rat Fc alpha/mu R but also in polymeric Ig receptor (poly-IgR), another Fc receptor for IgA and IgM. These results suggest that IgA and IgM bind to an epitope in the conserved amino acids in the Ig-like domain of Fc alpha/mu R as well as poly-IgR. (c) 2006 Elsevier Inc. All rights reserved.