Suenaga R, Mitamura K, Abdou N I
Immunology Research Laboratory, St. Luke's Hospital, Kansas City, Missouri 64111, USA.
Clin Immunol Immunopathol. 1998 Jan;86(1):72-80. doi: 10.1006/clin.1997.4448.
Binding and structural characteristics of human IgMk anti-ssDNA antibody 7B3 were determined. 7B3 was derived from Epstein-Barr virus-transformed peripheral blood B cells of a lupus nephritis patient. Purified 7B3 bound ssDNA from various species, but not dsDNA or structurally unrelated antigens. The relative avidity of 7B3 was high in comparison with IgM anti-DNA antibodies previously described by other investigators. Sequence analysis showed that 7B3 used VH26/D35/JH3 and Humkv328h5/JK1 germline genes, and had a few mutations in the complementarity determining regions (CDRs). No arginine was expressed in the heavy-chain CDR3. However, the putative DNA contact sites, based on the previous crystallographic and computer modeling studies, were occupied by mutated or germline-derived basic and polar amino acids. These results suggest that a minimally mutated IgM anti-ssDNA antibody with a paucity of arginines could display monospecificity and high avidity if DNA-binding amino acids are enriched at the critical DNA contact sites.
确定了人IgMκ抗单链DNA抗体7B3的结合和结构特征。7B3源自一名狼疮性肾炎患者的爱泼斯坦-巴尔病毒转化的外周血B细胞。纯化的7B3能结合来自各种物种的单链DNA，但不能结合双链DNA或结构不相关的抗原。与其他研究者先前描述的IgM抗DNA抗体相比，7B3的相对亲和力较高。序列分析表明，7B3使用VH26/D35/JH3和Humkv328h5/JK1胚系基因，并且在互补决定区（CDR）中有一些突变。重链CDR3中未表达精氨酸。然而，基于先前的晶体学和计算机建模研究，假定的DNA接触位点被突变的或源自胚系的碱性和极性氨基酸占据。这些结果表明，如果关键的DNA接触位点富含DNA结合氨基酸，那么一种精氨酸含量少、突变程度低的IgM抗单链DNA抗体可能表现出单特异性和高亲和力。
