Terness P, Navolan D, Moroder L, Siedler F, Weyher E, Kohl I, Dufter C, Welschof M, Drugarin D, Schneider F, Opelz G
Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Germany.
J Immunol. 1996 Nov 1;157(9):4251-7.
Natural anti-IgG autoantibodies are found both in healthy individuals and in patients with certain diseases. One group of these Abs recognizes epitopes located in the F(ab')2 region of the IgG molecule. The immunoregulatory role of these Abs in healthy individuals, graft rejection, and disease was previously studied, usually with a focus on the characterization of anti-idiotypic Abs. In the present study, we characterize the epitope recognized by an anti-F(ab')2gamma autoantibody of the IgA isotype, which occurs in the serum of healthy individuals and kidney transplant recipients. The autoantibody described herein reacts strongly with F(ab')2gamma but only poorly with Fab(gamma) fragments, a binding pattern pointing to an epitope located in the hinge region. Using synthetic peptides, we identified a conformational epitope that overlaps the middle and part of the lower hinge region. Structural analyses of peptide constructs showed that a defined conformation of the first three residues of the lower hinge is required for a full expression of the epitope. Binding of IgA to the hinge region of IgG1 covers part of the physiologically active Fc domain, immobilizes the Fab arms, and thereby can be expected to exert immunoregulatory functions.
天然抗IgG自身抗体在健康个体和某些疾病患者中均有发现。其中一组此类抗体识别位于IgG分子F(ab')2区域的表位。此前对这些抗体在健康个体、移植排斥反应和疾病中的免疫调节作用进行了研究，通常侧重于抗独特型抗体的特性描述。在本研究中，我们对一种IgA同种型的抗F(ab')2γ自身抗体所识别的表位进行了特性分析，该抗体存在于健康个体和肾移植受者的血清中。本文所述的自身抗体与F(ab')2γ强烈反应，但与Fab(γ)片段反应较弱，这种结合模式表明表位位于铰链区。通过合成肽，我们鉴定出一个与铰链区中部和下部部分重叠的构象表位。肽构建体的结构分析表明，铰链区下部前三个残基的特定构象是表位充分表达所必需的。IgA与IgG1铰链区的结合覆盖了部分生理活性Fc结构域，固定了Fab臂，因此有望发挥免疫调节功能。
