Functional analysis of activated C1s, a subcomponent of the first component of human complement, by monoclonal antibodies.
Functional analysis of activated C1s, a subcomponent of the first component of human complement, by monoclonal antibodies.
复制标题
通过单克隆抗体对活化的 C1（人类补体第一成分的亚成分）进行功能分析。
作者：
M. Matsumoto;K. Nagaki
用M365、M81和M241三种鼠抗人C1s的单抗分析了C1s的结构与酶活性的关系。M365和M81识别C1s重链上的不同表位，可与C1s结合，也可与C1s结合。C1s的C4裂解活性被M81完全阻断，并被M365部分阻断。虽然M81部分抑制了C1S的C2裂解活性，但M365未观察到阻断作用。两种抗体对C1S的酯解活性均无影响。这些结果表明，C1s上的C4和C2结合位点位于重链上，它们是不同的。M241只能与C1s结合，C1s是C1s的一种活性形式。C1s还原后，M241与C1s的重链和轻链均不发生反应。M241显著降低了C1S的酯解活性。此外，M241不仅阻断了C1s对C4和C2的切割，而且还阻断了C1s和C1失活剂的复合体的形成。从这些观察结果中，我们认为M241与C1s的活性中心发生反应，C1s的重链和轻链都参与了活性中心的组成。
Three mouse monoclonal antibodies (M365, M81, and M241) directed against human C1s were used to analyze the structure of C1s related to the enzymatic activity. M365 and M81 recognized different epitopes on the heavy chain of C1s and could bind to C1s, as well as to C1s. The C4 cleaving activity of C1s was completely blocked by M81 and was partially blocked by M365. Although the C2 cleaving activity of C1s was partially inhibited by M81, no blocking was observed with M365. Both antibodies had no effect on the esterolytic activity of C1s. These results indicate that the C4 and C2 binding sites on C1s reside in the heavy chain, and they are distinct from each other. M241 could bind only to C1s, an active form of C1s. After reduction of C1s, M241 could not react with either heavy or light chain of C1s. The esterolytic activity of C1s was markedly reduced by M241. Furthermore, M241 blocked not only the cleavage of C4 and C2 by C1s but also the complex formation of C1s and C1 inactivator. From these observations, we suggest that M241 reacts with the active site of C1s, and both heavy and light chains of C1s participate in the composition of the active site.