Cleavage of the human immunoglobulin A1 (IgA1) hinge region by IgA1 proteases requires structures in the Fc region of IgA
Cleavage of the human immunoglobulin A1 (IgA1) hinge region by IgA1 proteases requires structures in the Fc region of IgA
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DOI：
10.1128/iai.71.5.2563-2570.2003
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发表时间：
2003-05-01
影响因子：
3.1
通讯作者：
Morrison, SL
中科院分区：
文献类型：
--
作者：
Chintalacharuvu, KR;Chuang, PD;Morrison, SL
分泌型免疫球蛋白A（伊加）保护粘膜表面免受吸入和摄入的病原体的侵害。许多病原性细菌产生在IgA 1的铰链中切割的IgA 1蛋白酶，从而将Fab区与Fc区分离并使伊加无效。在这里，我们发现流感嗜血杆菌1型和淋病奈瑟菌2型IgA 1蛋白酶在IgA 1或IgA 2 m的恒定区中切割IgA 1铰链（1），但在IgG 2中不切割。C（alpha）2和C（alpha）3都是H裂解IgA 1铰链所必需的，但C（alpha）1不是。influenzae和N.淋病蛋白酶。虽然野生型IgA 1和仅含有O-连接聚糖的第一个GaINAc残基的IgA 1之间的切割动力学没有差异，但Fc中不存在N-连接聚糖增加了N.淋病蛋白酶切割IgA 1铰链。综上所述，这些结果表明，除了IgA 1铰链外，伊加Fc区的结构是H. influenzae和N.淋病蛋白酶。
Secretory immunoglobulin A (IgA) protects the mucosal surfaces against inhaled and ingested pathogens. Many pathogenic bacteria produce IgA1 proteases that cleave in the hinge of IgA1, thus separating the Fab region from the Fc region and making IgA ineffective. Here, we show that Haemophilus influenzae type 1 and Neisseria gonorrhoeae type 2 IgA1 proteases cleave the IgA1 hinge in the context of the constant region of IgA1 or IgA2m (1) but not in the context of IgG2. Both C(alpha)2 and C(alpha)3 but not C(alpha)1 are required for the cleavage of the IgA1 hinge by H. influenzae and N. gonorrhoeae proteases. While there was no difference in the cleavage kinetics between wild-type IgA1 and IgA1 containing only the first GaINAc residue of the O-linked glycans, the absence of N-linked glycans in the Fc increased the ability of the N. gonorrhoeae protease to cleave the IgA1 hinge. Taken together, these results suggest that, in addition to the IgA1 hinge, structures in the Fc region of IgA are required for the recognition and cleavage of IgA1 by the H. influenzae and N. gonorrhoeae proteases.