Immunoglobulin-binding sites of human Fc alpha RI (CD89) and bovine Fc gamma 2R are located in their membrane-distal extracellular domains

To localize the immunoglobulin (Ig)-binding regions of the human Fc alpha r eceptor (Fc alpha RI, CD89) and the bovine Fc gamma 2 receptor (bFc gamma 2 R), chimeric receptors were generated by exchanging comparable regions betw een these two proteins Fc alpha RI and bFc gamma 2R are highly homologous a nd are more closely related to each other than to other human and bovine Fc Rs. Nevertheless, they are functionally distinct in that Fc alpha RI binds human IgA (hIgA) but not bovine IgG2 (bIgG2), whereas bFc gamma 2R binds bI gG2 but not hIgA. Fc alpha RI and bFc gamma 2R possess extracellular region s consisting of two Ig-like domains, a membrane-distal extracellular domain (EC1), a membrane-proximal EC domain (EC2), a transmembrane region, and a shea cytoplasmic tail. Chimeras constructed by exchanging complete domains between these two receptors were transfected to COS-1 cells and assayed for their ability to bind hIgA- or bIgG2-coated beads. The results showed that the Ig-binding site of both Fc alpha RI and bFc gamma 2R is located within EC1. Supporting this observation, monoclonal antibodies that blocked IgA b inding to Fc alpha RI were found to recognize epitopes located in this doma in. In terms of FcR-Ig interactions characterized thus far, this location i s unique and surprising because it has been shown previously that leukocyte Fc gamma Rs and Fc epsilon RI bind Ig via sites principally located in the ir EC2 domains.