| Summary: | To localize the immunoglobulin (Ig)-binding regions of the human Fcα receptor (FcαRI, CD89) and the bovine Fcγ2 receptor (bFcγ2R), chimeric receptors were generated by exchanging comparable regions between these two proteins. FcαRI and bFcγ2R are highly homologous and are more closely related to each other than to other human and bovine FcRs. Nevertheless, they are functionally distinct in that FcαRI binds human IgA (hIgA) but not bovine IgG2 (bIgG2), whereas bFcγ2R binds bIgG2 but not hIgA. FcαRI and bFcγ2R possess extracellular regions consisting of two Ig-like domains, a membrane-distal extracellular domain (EC1), a membrane-proximal EC domain (EC2), a transmembrane region, and a short 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 FcαRI and bFcγ2R is located within EC1. Supporting this observation, monoclonal antibodies that blocked IgA binding to FcαRI were found to recognize epitopes located in this domain. In terms of FcR–Ig interactions characterized thus far, this location is unique and surprising because it has been shown previously that leukocyte FcγRs and FcεRI bind Ig via sites principally located in their EC2 domains.
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