J. Exp. Med., Volume 189, Number 11, June 7, 1999 1715-1722

Immunoglobulin-binding Sites of Human FcRI (CD89) and Bovine Fc2R Are Located in their Membrane-distal Extracellular Domains

By H. Craig Morton,^* Ger van Zandbergen, Cees van Kooten, Chris J. Howard,^§ Jan G. J. van de Winkel, and Per Brandtzaeg^*

From the ^* Laboratory of Immunohistochemistry and Immunopathology (LIIPAT), The National Hospital, University of Oslo, Rikshospitalet, N-0027 Oslo, Norway; the  Department of Nephrology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; the ^§ Division of Immunology and Pathology, The Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; and the  Department of Immunology and Medarex Europe, University Hospital Utrecht, 3584 CX Utrecht, The Netherlands

To localize the immunoglobulin (Ig)-binding regions of the human Fc receptor (FcRI, CD89) and the bovine Fc2 receptor (bFc2R), chimeric receptors were generated by exchanging comparable regions between these two proteins. FcRI and bFc2R 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 FcRI binds human IgA (hIgA) but not bovine IgG2 (bIgG2), whereas bFc2R binds bIgG2 but not hIgA. FcRI and bFc2R 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 FcRI and bFc2R is located within EC1. Supporting this observation, monoclonal antibodies that blocked IgA binding to FcRI 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 FcRs and FcRI bind Ig via sites principally located in their EC2 domains.

Fc receptor;  CD89;  bovine Fc2 receptor;  immunoglobulin A;  myeloid

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