Chintalacharuvu Koteswara R, Chuang Philip D, Dragoman Ashley, Fernandez Christine Z, Qiu Jiazhou, Plaut Andrew G, Trinh K Ryan, Gala Françoise A, Morrison Sherie L
Department of Microbiology, Immunology and Molecular Genetics and The Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.
Infect Immun. 2003 May;71(5):2563-70. doi: 10.1128/IAI.71.5.2563-2570.2003.
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 GalNAc 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.
分泌型免疫球蛋白A（IgA）可保护黏膜表面免受吸入和摄入病原体的侵害。许多致病细菌会产生IgA1蛋白酶，该酶在IgA1的铰链区进行切割，从而将Fab区域与Fc区域分离，使IgA失效。在此，我们表明，1型流感嗜血杆菌和2型淋病奈瑟菌的IgA1蛋白酶在IgA1或IgA2m(1)恒定区的背景下切割IgA1铰链区，但不在IgG2的背景下切割。流感嗜血杆菌和淋病奈瑟菌蛋白酶切割IgA1铰链区需要C(α)2和C(α)3，但不需要C(α)1。虽然野生型IgA1与仅含有O-连接聚糖第一个GalNAc残基的IgA1在切割动力学上没有差异，但Fc区N-连接聚糖的缺失增加了淋病奈瑟菌蛋白酶切割IgA1铰链区的能力。综上所述，这些结果表明，除了IgA1铰链区外，IgA的Fc区结构对于流感嗜血杆菌和淋病奈瑟菌蛋白酶识别和切割IgA1也是必需的。
