Membrane cofactor protein (MCP; CD46). Isoforms differ in protection against the classical pathway of complement.
Membrane cofactor protein (MCP; CD46). Isoforms differ in protection against the classical pathway of complement.
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DOI：
10.4049/jimmunol.156.11.4415
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发表时间：
1996-06
影响因子：
4.4
通讯作者：
M. Liszewski;J. Atkinson
中科院分区：
文献类型：
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作者：
M. Liszewski;J. Atkinson
膜辅因子蛋白（MCP；CD46）是一种广泛分布的 C3b/C4b 结合糖蛋白，可抑制宿主细胞上的补体激活。 MCP 主要表达为由单个基因的选择性剪接产生的四种亚型。差异在于 O-糖基化和细胞质尾部的结构域。同种型的组织特异性表达和细胞质尾介导的前体的差异加工表明同种型变异具有生物学意义。这些实验的目的是表征四种常见表达亚型的补体抑制谱。具有较大 O-糖基化结构域的 MCP 同工型 (BC) 比 C 同工型更有效地结合 C4b，而 C 同工型在该区域较小且糖基化程度较低。此外，对具有相同拷贝数的转染异构体的单个克隆进行的细胞保护测定表明，BC 异构体还在经典途径介导的系统中提供增强的保护，并且比 C 异构体更有效地裂解细胞结合的 C4b。总而言之，这些数据表明 BC 同工型优先保护免受补体经典途径的影响。这些发现表明同种型变异的生理作用，并对在异种移植等领域使用 MCP 同种型作为补体抑制剂具有治疗意义。
Membrane cofactor protein (MCP; CD46) is a widely distributed C3b/C4b-binding glycoprotein that inhibits complement activation on host cells. MCP is expressed primarily as four isoforms that arise by alternative splicing of a single gene. The differences reside in the domains for O-glycosylation and cytoplasmic tails. Tissue-specific expression of isoforms and the differential processing of precursors mediated by the cytoplasmic tails suggest that isoform variations are biologically significant. The goal of these experiments was to characterize the complement inhibitory profile of the four commonly expressed isoforms. The MCP isoforms (BC) with a larger O-glycosylation domain bound C4b more efficiently than the C isoforms, which are smaller and less glycosylated in this region. Additionally, cytoprotection assays of individual clones of transfected isoforms bearing equivalent copy numbers demonstrated that the BC isoforms also provided enhanced protection in a classical pathway-mediated system and cleaved cell-bound C4b more efficiently than the C isoforms. Taken together, these data demonstrate that BC isoforms preferentially protect against the classical pathway of complement. Such findings indicate a physiologic role for isoform variation and have therapeutic implications for use of MCP isoforms as complement inhibitors in such areas as xenotransplantation.