Domain deletions in the human polymeric Ig receptor disclose differences between its dimeric IgA and pentameric IgM interaction.
The human polymeric Ig receptor (pIgR), or transmembrane secretory component, is basolaterally expressed on secretory epithelial cells; its function is to transport externally J chain-containing dimeric IgA and pentameric IgM. The ligand-binding extracellular part of this receptor contains five disulfide-stabilized domains which show considerable homology with the variable domains of Ig chains. The N-terminal domain 1 (D1) mediates the initial noncovalent ligand interaction. In this study we made deletions of the human pIgR D2 and D3 (pIgRDelta2,3), or D4 and D5 (pIgRDelta4,5), to investigate the influence of these domains in receptor binding and transport of dimeric IgA and pentameric IgM across MDCK cells transfected with the truncated receptors. Both mutants were found to bind pentameric IgM, but only pIgRDelta4,5 bound dimeric IgA. These results showed that the two ligands interact differently with human pIgR; binding of pentameric IgM apparently depends fully on strong interactions with D1, while binding of dimeric IgA in addition depends on elements within D2 and / or D3 to support the initial noncovalent binding to D1. Moreover, our studies imply that dimeric human IgA binds differently to pIgR from various species. This observation cautions against interpretation of functional studies performed with non-homologous receptor-ligand pairs.
Norderhaug
I N
IN
Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, University of Oslo, Rikshospitalet, Oslo, Norway.
Johansen
F E
FE
Krajci
P
P
Brandtzaeg
P
P
D000818:Animals; D001666:Binding Sites, Antibody / Q000235:genetics; D002478:Cells, Cultured; D019281:Dimerization; D004285:Dogs; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D019056:Receptors, Polymeric Immunoglobulin / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D014162:Transfection
D007070:Immunoglobulin A; D007075:Immunoglobulin M; D010446:Peptide Fragments; D019056:Receptors, Polymeric Immunoglobulin