Structure of the secretory immunoglobulin A core

Science ◽  
2020 ◽  
Vol 367 (6481) ◽  
pp. 1008-1014 ◽  
Author(s):  
Nikit Kumar ◽  
Christopher P. Arthur ◽  
Claudio Ciferri ◽  
Marissa L. Matsumoto
Keyword(s):  
Immunoglobulin A ◽  
Secretory Component ◽  
Polymeric Immunoglobulin Receptor ◽  
Secretory Immunoglobulin A ◽  
First Line ◽  
Immunoglobulin Receptor ◽  
Host Protection ◽  
Luminal Side ◽  
Mucosal Pathogens ◽  
Secretory Immunoglobulin

Secretory immunoglobulin A (sIgA) represents the immune system’s first line of defense against mucosal pathogens. IgAs are transported across the epithelium, as dimers and higher-order polymers, by the polymeric immunoglobulin receptor (pIgR). Upon reaching the luminal side, sIgAs mediate host protection and pathogen neutralization. In recent years, an increasing amount of attention has been given to IgA as a novel therapeutic antibody. However, despite extensive studies, sIgA structures have remained elusive. Here, we determine the atomic resolution structures of dimeric, tetrameric, and pentameric IgA-Fc linked by the joining chain (JC) and in complex with the secretory component of the pIgR. We suggest a mechanism in which the JC templates IgA oligomerization and imparts asymmetry for pIgR binding and transcytosis. This framework will inform the design of future IgA-based therapeutics.

scholarly journals Structural insights into secretory immunoglobulin A and its interaction with a pneumococcal adhesin

2020 ◽  
Author(s):  
Yuxin Wang ◽  
Guopeng Wang ◽  
Yaxin Li ◽  
Hao Shen ◽  
Huarui Chu ◽  
...  
Keyword(s):  
Specific Interaction ◽  
Immunoglobulin A ◽  
Underlying Mechanism ◽  
Secretory Component ◽  
Secretory Immunoglobulin A ◽  
Immunoglobulin Receptor ◽  
J Chain ◽  
Cryo Electron Microscopy ◽  
Structural Insights ◽  
Secretory Immunoglobulin

AbstractSecretory Immunoglobulin A (SIgA) is the most abundant antibody at the mucosal surface. SIgA possesses two additional subunits besides IgA: the joining chain (J-chain) and secretory component (SC). SC is the ectodomain of the polymeric immunoglobulin receptor (pIgR), which functions to transport IgA to the mucosa. The underlying mechanism of how the J-chain and pIgR/SC facilitates the assembly and secretion of SIgA remains to be understood. During the infection of Streptococcus pneumoniae, a pneumococcal adhesin SpsA hijacks SIgA and unliganded pIgR/SC to evade host defense and gain entry to human cells. How SpsA specifically targets SIgA and pIgR/SC also remains unclear. Here we report a cryo-electron microscopy structure of the Fc region of human IgA1 (Fcα) in complex with J-chain and SC (Fcα-J-SC), which reveals the organization principle of SIgA. We also present the structure of Fcα-J-SC in complex with SpsA, which uncovers the specific interaction between SpsA and human pIgR/SC. These results advance the molecular understanding of SIgA and shed light on the pathogenesis of S. pneumoniae.

Column enzyme immunoassay for secretory immunoglobulin A in serum.

1983 ◽  
Vol 29 (1) ◽  
pp. 151-153 ◽  
Author(s):  
R Yamamoto ◽  
S Kimura ◽  
S Hattori ◽  
Y Ishiguro ◽  
K Kato
Keyword(s):  
Enzyme Immunoassay ◽  
Sodium Carbonate Solution ◽  
Solid Phase ◽  
Immunoglobulin A ◽  
Enzyme Reaction ◽  
Secretory Component ◽  
Secretory Immunoglobulin A ◽  
Serum Samples ◽  
Sepharose 4B ◽  
Secretory Immunoglobulin

Abstract This enzyme immunoassay for specific measurement of secretory immunoglobulin A concentrations in human serum involves use of a small chromatographic column as a solid-phase. Serum samples are incubated for 2 h with beta-D-galactosidase-labeled antibody to secretory component, then passed through a 0.1-mL Sepharose 4B column containing antibodies to human immunoglobulin A. After the column is washed to remove the unbound label, the buffer in the column is replaced by a solution of o-nitrophenyl-beta-D-galactoside (a beta-D-galactosidase substrate) and incubated at 25 degrees C overnight. The enzyme reaction is stopped by washing the column with sodium carbonate solution, and the absorbance of the eluate is measured at 420 nm. The concentration of secretory immunoglobulin A can be determined with a minimum detectable sensitivity of 3 mg/L, without interference from free immunoglobulin A and secretory component in the same samples.

scholarly journals Specialization of mucosal immunoglobulins in pathogen control and microbiota homeostasis occurred early in vertebrate evolution

2020 ◽  
Vol 5 (44) ◽  
pp. eaay3254 ◽  
Author(s):  
Zhen Xu ◽  
Fumio Takizawa ◽  
Elisa Casadei ◽  
Yasuhiro Shibasaki ◽  
Yang Ding ◽  
...  
Keyword(s):  
Rainbow Trout ◽  
Tissue Damage ◽  
Immunoglobulin A ◽  
Secretory Immunoglobulin A ◽  
Central Question ◽  
Vertebrate Species ◽  
Mucosal Surfaces ◽  
Pathogen Control ◽  
Mucosal Pathogens ◽  
Secretory Immunoglobulin

Although mammalian secretory immunoglobulin A (sIgA) targets mucosal pathogens for elimination, its interaction with the microbiota also enables commensal colonization and homeostasis. This paradoxical requirement in the control of pathogens versus microbiota raised the question of whether mucosal (secretory) Igs (sIgs) evolved primarily to protect mucosal surfaces from pathogens or to maintain microbiome homeostasis. To address this central question, we used a primitive vertebrate species (rainbow trout) in which we temporarily depleted its mucosal Ig (sIgT). Fish devoid of sIgT became highly susceptible to a mucosal parasite and failed to develop compensatory IgM responses against it. IgT depletion also induced a profound dysbiosis marked by the loss of sIgT-coated beneficial taxa, expansion of pathobionts, tissue damage, and inflammation. Restitution of sIgT levels in IgT-depleted fish led to a reversal of microbial translocation and tissue damage, as well as to restoration of microbiome homeostasis. Our findings indicate that specialization of sIgs in pathogen and microbiota control occurred concurrently early in evolution, thus revealing primordially conserved principles under which primitive and modern sIgs operate in the control of microbes at mucosal surfaces.

Sign in / Sign up

Export Citation Format

Share Document