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针对裂殖子表面抗原的单克隆IgG的Fab片段可抑制诺氏疟原虫对红细胞的入侵。

The Fab fragments of monoclonal IgG to a merozoite surface antigen inhibit Plasmodium knowlesi invasion of erythrocytes.

作者信息

Thomas A W, Deans J A, Mitchell G H, Alderson T, Cohen S

出版信息

Mol Biochem Parasitol. 1984 Oct;13(2):187-99. doi: 10.1016/0166-6851(84)90112-9.

DOI:10.1016/0166-6851(84)90112-9
PMID:6513992
Abstract

Two rat monoclonal antibodies (both IgG2a isotype and having closely related specificities) and a pool of rhesus immune IgG, all of which inhibit Plasmodium knowlesi merozoite invasion of rhesus erythrocytes, have been studied before and after proteolytic digestion. The F(ab')2 and Fab fragments of both rat monoclonal antibodies show considerably enhanced inhibition of merozoite invasion as compared with the intact IgG. Inhibition by monovalent fragments indicates that these antibodies are not dependent upon merozoite agglutination and may act by blocking merozoite attachment to the specific red cell receptor. The fact that the inhibitory activities of F(ab')2 and Fab are equally enhanced on a weight basis, as compared with IgG, suggests that the removal of Fc may reduce electrostatic repulsion between antibody and merozoite surface, both of which are negatively charged at neutral pH. By contrast, papain digestion of polyclonal IgG derived from an immunised rhesus pool markedly reduces its inhibitory activity. This suggests that much of the inhibition mediated by polyclonal IgG results from merozoite agglutination and that the specificity of the rat inhibitory monoclonal antibodies is poorly represented in the immune pool. The P. knowlesi antigen reactive with the inhibitory monoclonal antibodies is known to be synthesized as a minor 66 kDa polypeptide during the last 1.5 h. of schizont development and is processed to smaller products (44 and 42 kDa) present on the merozoite surface. The present results suggest that this antigen may have particular interest as a vaccine against P. knowlesi malaria.

摘要

两种大鼠单克隆抗体(均为IgG2a亚型且具有密切相关的特异性)以及一组恒河猴免疫IgG,它们均能抑制诺氏疟原虫裂殖子侵入恒河猴红细胞,对其进行蛋白水解消化前后均已开展研究。与完整的IgG相比,两种大鼠单克隆抗体的F(ab')2和Fab片段对裂殖子侵入的抑制作用显著增强。单价片段的抑制作用表明这些抗体不依赖于裂殖子凝集,可能通过阻断裂殖子与特定红细胞受体的结合来发挥作用。与IgG相比,F(ab')2和Fab的抑制活性在重量基础上同等增强,这一事实表明去除Fc可能会减少抗体与裂殖子表面之间的静电排斥,在中性pH条件下两者均带负电荷。相比之下,来自免疫恒河猴血清的多克隆IgG经木瓜蛋白酶消化后其抑制活性显著降低。这表明多克隆IgG介导的大部分抑制作用源于裂殖子凝集,并且免疫血清中大鼠抑制性单克隆抗体的特异性表现不佳。已知与抑制性单克隆抗体反应的诺氏疟原虫抗原在裂殖体发育的最后1.5小时作为一种次要的66 kDa多肽合成,并被加工成裂殖子表面存在的较小产物(44 kDa和42 kDa)。目前的结果表明,这种抗原作为抗诺氏疟原虫疟疾的疫苗可能具有特殊意义。

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