Tamm A, Kister A, Nolte K U, Gessner J E, Schmidt R E
Department of Clinical Immunology, Hannover Medical School, Konstanty-Gutschow Stra sse 8, 30625 Hannover, Federal Republic of Germany.
J Biol Chem. 1996 Feb 16;271(7):3659-66. doi: 10.1074/jbc.271.7.3659.
Fc gamma receptors for the Fc part of IgG are the mediators for antibody effector functions. FcgammaRIII and FcgammaRII are low affinity receptors that, through the interaction with immune complexes, initiate a variety of immunological responses, such as phagocytosis, antibody-dependent cellular cytotoxicity, and release of inflammatory mediators. We set out to define the IgG binding site on human FcgammaRIII. We assumed that potential beta-turns in Ig-like domains are the most probable determinants for ligand binding, and chimeric FcgammaRIIIB/FcepsilonRI receptors as well as single residue mutants were constructed in these regions of FcgammaRIIIB. Substitution of four amino acids in the membrane-proximal domain (Gln126, Arg156, Lys162, Val164) resulted in decreased binding of human IgG1. Lys162 and Val164 were found also to be crucial for the interaction with the IgG-binding inhibitory monoclonal antibody 3G8. In a putative three-dimensional model constructed in this study, these residues map on the CC loop (Gln126), on F beta-sheet (Arg156), and on the FG loop (Lys162, Val164). Our data are consistent with the study about human FcgammaRII (Hulett, M. D., Witort, E., Brinkworth, R. I., McKenzie, I. F. C., and Hogarth, P. M. (1994) J. Biol. Chem. 269, 15287-15293), suggesting that common structural determinants, i.e. FG loop or the GFC surface of the membrane-proximal domain, can be involved in interactions with IgG by both low affinity receptor classes FcgammaRII and FcgammaRIII.
针对IgG的Fc部分的Fcγ受体是抗体效应功能的介质。FcγRIII和FcγRII是低亲和力受体，它们通过与免疫复合物相互作用，引发多种免疫反应，如吞噬作用、抗体依赖性细胞毒性以及炎症介质的释放。我们着手确定人FcγRIII上的IgG结合位点。我们假定Ig样结构域中潜在的β转角最有可能是配体结合的决定因素，并在FcγRIIIB的这些区域构建了嵌合的FcγRIIIB/FcεRI受体以及单残基突变体。膜近端结构域中的四个氨基酸（Gln126、Arg156、Lys162、Val164）被替换后，人IgG1的结合减少。还发现Lys162和Val164对于与IgG结合抑制性单克隆抗体3G8的相互作用至关重要。在本研究构建的一个假定三维模型中，这些残基位于CC环（Gln126）、Fβ折叠（Arg156）以及FG环（Lys162、Val164）上。我们的数据与关于人FcγRII的研究（Hulett, M. D., Witort, E., Brinkworth, R. I., McKenzie, I. F. C., and Hogarth, P. M. (1994) J. Biol. Chem. 269, 15287 - 15293）一致，表明共同的结构决定因素，即膜近端结构域的FG环或GFC表面，可能参与低亲和力受体FcγRII和FcγRIII与IgG的相互作用。
