Fine specificity of ligand-binding domain 1 in the polymeric Ig receptor: Importance of the CDR2-containing region for IgM interaction

The human polymeric Ig receptor (pIgR), also called transmembrane secretory component, is expressed basolaterally on exocrine epithelia, and mediates specific external transport of dimeric IgA and pentameric IgM, The extracel lular part of pIgR consists of five Ig-like domains (D1-D5), and a highly c onserved D1 region appears to mediate the initial noncovalent ligand intera ction. While the human pIgR binds both dimeric IgA and pentameric IgM with high affinity, the rabbit counterpart has virtually no binding capacity for pentameric IgM, This remarkable disparity constitutes evidence that the bi nding site of the two ligands differs with regard to essential receptor con tact elements. Therefore, we expressed human/rabbit chimeric pIgRs in Madin -Darby canine kidney cells and found that human pIgR D1 is crucial for the interaction with pentameric IgM when placed in the context of a full-length receptor regardless of its backbone species. D1 contains three complementa rity-determining region-like loops (CDR1-3), and to further map human D1 re gions involved in pentameric IgM binding, we transfected Madin-Darby canine kidney cells with human/rabbit chimeric receptors in which the regions con taining the CDR-like loops had been interchanged. Our results showed that t he region containing the CDR2-like loop is the most essential for pentameri c IgM binding. The region containing the CDR1-like loop also contributed su bstantially to this interaction, whereas only little contribution was provi ded by the region containing the CDR3-like loop, although it appeared to be necessary for maximal pentameric IgM binding.