Centocor R&D, Inc., 145 King of Prussia Road, Radnor, PA 19087, USA.
Mol Immunol. 2010 Aug;47(14):2422-6. doi: 10.1016/j.molimm.2010.05.002.
A chimeric antibody was constructed from two unrelated antibodies by combining their heavy and light chains. The "double chimera" consists of the mouse variable regions of different specificity (IL-13 and EMMPRIN) and the constant regions of different origin (mouse and human). The Fab fragment of this chimeric antibody was expressed in mammalian cells, and the crystal structure was determined at 1.6A resolution. Despite a large number of amino acid substitutions in the double chimera with respect to the parent antibodies, the heavy and light chains associate into a stable molecule. Comparison to the structure of one of the parent antibodies reveals that the variable domain interface, as well as the conformation of antigen-binding loops, is preserved without major rearrangements due to conservation of amino acids in key positions. Comparison to the structures of the all-human and all-mouse constant domains indicates a remarkable plasticity of the inter-chain interface that can tolerate residue relocations of up to 6A.
通过将重链和轻链组合，从两个不相关的抗体构建了嵌合抗体。“双嵌合体”由不同特异性的鼠可变区（IL-13 和 EMMPRIN）和不同来源的恒定区（鼠和人）组成。该嵌合抗体的 Fab 片段在哺乳动物细胞中表达，并在 1.6A 分辨率下确定了晶体结构。尽管与亲本抗体相比，双嵌合体中有大量的氨基酸取代，但重链和轻链仍能结合成稳定的分子。与其中一个亲本抗体的结构比较表明，由于关键位置的氨基酸保守，可变区界面以及抗原结合环的构象得以保持，没有发生大的重排。与全人源和全鼠源恒定区的结构比较表明，链间界面具有显著的可变性，可耐受多达 6A 的残基重定位。
