Røe M, Norderhaug I N, Brandtzaeg P, Johansen F E
Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, University of Oslo, The National Hospital, Rikshospitalet, Oslo, Norway.
J Immunol. 1999 May 15;162(10):6046-52.
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 extracellular part of pIgR consists of five Ig-like domains (D1-D5), and a highly conserved D1 region appears to mediate the initial noncovalent ligand interaction. 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 binding site of the two ligands differs with regard to essential receptor contact 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 complementarity-determining region-like loops (CDR1-3), and to further map human D1 regions involved in pentameric IgM binding, we transfected Madin-Darby canine kidney cells with human/rabbit chimeric receptors in which the regions containing the CDR-like loops had been interchanged. Our results showed that the region containing the CDR2-like loop is the most essential for pentameric IgM binding. The region containing the CDR1-like loop also contributed substantially to this interaction, whereas only little contribution was provided by the region containing the CDR3-like loop, although it appeared to be necessary for maximal pentameric IgM binding.
人多聚免疫球蛋白受体（pIgR），也称为跨膜分泌成分，在外分泌上皮细胞的基底外侧表达，并介导二聚体IgA和五聚体IgM的特异性外向转运。pIgR的细胞外部分由五个免疫球蛋白样结构域（D1-D5）组成，高度保守的D1区域似乎介导最初的非共价配体相互作用。虽然人pIgR以高亲和力结合二聚体IgA和五聚体IgM，但兔的相应受体对五聚体IgM几乎没有结合能力。这种显著差异证明，两种配体的结合位点在关键受体接触元件方面有所不同。因此，我们在犬肾细胞中表达了人/兔嵌合pIgR，发现人pIgR D1在全长受体的背景下，无论其主干物种如何，对于与五聚体IgM的相互作用都至关重要。D1包含三个互补决定区样环（CDR1-3），为了进一步定位参与五聚体IgM结合的人D1区域，我们用包含类CDR环的区域已互换的人/兔嵌合受体转染了犬肾细胞。我们的结果表明，包含类CDR2环的区域对于五聚体IgM结合最为关键。包含类CDR1环的区域对这种相互作用也有很大贡献，而包含类CDR3环的区域贡献很小，尽管它似乎是最大程度结合五聚体IgM所必需的。
