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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7 June 1999
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June 07 1999
Immunoglobulin-binding Sites of Human FcαRI (CD89) and Bovine Fcγ2R Are Located in their Membrane-distal Extracellular Domains
H. Craig Morton,
H. Craig Morton
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
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Ger van Zandbergen,
Ger van Zandbergen
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
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Cees van Kooten,
Cees van Kooten
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
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Chris J. Howard,
Chris J. Howard
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
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Jan G. J. van de Winkel,
Jan G. J. van de Winkel
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
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Per Brandtzaeg
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
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H. Craig Morton
,
Ger van Zandbergen
,
Cees van Kooten
,
Chris J. Howard
,
Jan G. J. van de Winkel
,
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
Address correspondence to H. Craig Morton, LIIPAT, Rikshospitalet, N-0027, Oslo, Norway. Phone: 47-22-86-86-31; Fax: 47-22-11-22-61; E-mail: [email protected]
Note added in proof. A recent report by Wines et al. (J. Immunol. 1999. 162:2146–2153) likewise identified the EC1 domain of FcαRI to be responsible for ligand binding.
Received:
December 24 1998
Revision Received:
March 29 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (11): 1715–1722.
Article history
Received:
December 24 1998
Revision Received:
March 29 1999
Citation
H. Craig Morton, Ger van Zandbergen, Cees van Kooten, Chris J. Howard, Jan G. J. van de Winkel, Per Brandtzaeg; Immunoglobulin-binding Sites of Human FcαRI (CD89) and Bovine Fcγ2R Are Located in their Membrane-distal Extracellular Domains . J Exp Med 7 June 1999; 189 (11): 1715–1722. doi: https://doi.org/10.1084/jem.189.11.1715
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