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骆驼科动物抗体库的发育

Antibody repertoire development in camelids.

作者信息

De Genst Erwin, Saerens Dirk, Muyldermans Serge, Conrath Katja

机构信息

Laboratory of Cellular & Molecular Immunology, Department of Molecular & Cellular Interactions, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Building E, Room 8.2, Pleinlaan 2, 1050 Brussel, Belgium.

出版信息

Dev Comp Immunol. 2006;30(1-2):187-98. doi: 10.1016/j.dci.2005.06.010.

Abstract

The humoral immune response of the Camelidae is unique as these animals are the only known mammals that seem to possess functional homodimeric heavy-chain antibodies besides the classical heteromeric antibodies composed of heavy (H) and light (L) chains. By definition, the heavy-chain antibodies lack the L-chain, and it was noticed that their H-chain is devoid of the typical first constant domain (CH1) and contains a dedicated variable domain, referred to as VHH. The VHH exon is assembled from separate V-D-J gene segments. The recombined VHH region is subjected to somatic hypermutations; however, the timing and actual mechanism of the class switch from mu to the dedicated gamma-isotype remains elusive. Interestingly, antigen-specific VHHs are easily retrieved after panning of a phage-displayed rearranged V-gene pool cloned from an immunised camelid. These single-domain antigen binding entities possess a number of biophysical properties that offer particular advantages in various medical and biotechnological applications.

摘要

骆驼科动物的体液免疫反应独特,因为这些动物是已知唯一除了由重链(H)和轻链(L)组成的经典异源二聚体抗体外,似乎还拥有功能性同型二聚体重链抗体的哺乳动物。根据定义,重链抗体缺乏轻链,并且人们注意到它们的重链没有典型的第一个恒定结构域(CH1),而是包含一个专门的可变结构域,称为VHH。VHH外显子由单独的V-D-J基因片段组装而成。重组后的VHH区域会经历体细胞超突变;然而,从μ类转换到专门的γ类同型的时间和实际机制仍然不清楚。有趣的是,从免疫骆驼科动物克隆的噬菌体展示重排V基因库淘选后,很容易获得抗原特异性VHH。这些单结构域抗原结合实体具有许多生物物理特性,在各种医学和生物技术应用中具有特殊优势。

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