Cleavage of the human immunoglobulin A1 (IgA1) hinge region by IgA1 proteases requires structures in the Fc region of IgA.
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.
Chintalacharuvu
Koteswara R
KR
Department of Microbiology, Immunology and Molecular Genetics and The Molecular Biology Institute, University of California, Los Angeles, California 90095, USA. kotec@lifesci.ucla.edu
Chuang
Philip D
PD
Dragoman
Ashley
A
Fernandez
Christine Z
CZ
Qiu
Jiazhou
J
Plaut
Andrew G
AG
Trinh
K Ryan
KR
Gala
Françoise A
FA
Morrison
Sherie L
SL
D006193:Haemophilus influenzae / Q000201:enzymology*; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry / Q000378:metabolism*; D009344:Neisseria gonorrhoeae / Q000201:enzymology*; D011134:Polysaccharides / Q000737:chemistry; D011487:Protein Conformation; D011961:Receptors, Fc / Q000737:chemistry* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*
C045281:IgA receptor; D007070:Immunoglobulin A; D011134:Polysaccharides; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase