致病性II型胶原特异性小鼠单克隆抗体CIIC1 Fab的晶体结构：结构与功能分析

The crystal structure of the pathogenic collagen type II-specific mouse monoclonal antibody CIIC1 Fab: structure to function analysis.

作者信息

Uysal Hüseyin, Sehnert Bettina, Nandakumar Kutty S, Böiers Ulrika, Burkhardt Harald, Holmdahl Rikard, Thunnissen Marjolein M G M

机构信息

Department of Molecular Biophysics, Lund University, Chemical Center, Box 124, SE 221 00, Lund, Sweden.

出版信息

Mol Immunol. 2008 Apr;45(8):2196-204. doi: 10.1016/j.molimm.2007.12.005. Epub 2008 Feb 1.

DOI:10.1016/j.molimm.2007.12.005

PMID:18241923

Abstract

Monoclonal anti-collagen type II antibody CIIC1 is an arthritogenic autoantibody, which induces arthritis in mice. We crystallized and solved the structure of CIIC1 Fab molecule. Analysis of structure revealed an interaction between the CDR regions of one Fab to the CH1 domain of another Fab, which resembles an antibody-antigen interaction. ELISA experiments confirmed the cross-reactivity of both the full CIIC1 antibody and a single chain Fv fragment to other anti-collagen antibodies which are of different isotypes and epitope specificity. The rheumatoid factor like reactivity of CIIC1 antibody together with its collagen type II specificity may explain the pathogenicity of this antibody.

摘要

单克隆抗II型胶原蛋白抗体CIIC1是一种致关节炎自身抗体，可在小鼠中诱发关节炎。我们对CIIC1 Fab分子进行了结晶并解析了其结构。结构分析显示，一个Fab的互补决定区（CDR）与另一个Fab的CH1结构域之间存在相互作用，这类似于抗体与抗原的相互作用。酶联免疫吸附测定（ELISA）实验证实，完整的CIIC1抗体和单链Fv片段与其他具有不同同种型和表位特异性的抗胶原蛋白抗体具有交叉反应性。CIIC1抗体的类风湿因子样反应性及其对II型胶原蛋白的特异性可能解释了该抗体的致病性。