Working Mechanism of Immunoglobulin A1 (IgA1) Protease: Cleavage of IgA1 Antibody to<i>Neisseria meningitidis</i>PorA Requires De Novo Synthesis of IgA1 Protease

Vidarsson, Gestur; Overbeeke, Natasja; Stemerding, Annette M.; Dobbelsteen, Germie van den; Ulsen, Peter van; Ley, Peter van der; Kilian, Mogens; Winkel, Jan G. J. van de

doi:10.1128/iai.73.10.6721-6726.2005

Cited by 23 publications

(18 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4). In humans, it is well known that IgA‐mediated mucosal immunity is compromised by certain pathogens such as Streptococcus pneumoniae , Haemophilus influenzae and Neisseria menigitidis , which produce proteases capable of cleaving IgA1, but not IgA2, in its hinge region [37]. As bovine IgG1 is the major antibody subclass in milk and mucosal immunity, we suggest that the IgG1 c sequence allele would be more susceptible to immune evasion by protease‐producing bacteria.…”

Section: Resultsmentioning

confidence: 85%

Structural Evidence for a New IgG1 Antibody Sequence Allele of Cattle

Saini¹,

Farrugia²,

Muthusamy³

et al. 2006

Scand J Immunol

View full text Add to dashboard Cite

Analysis of the heavy-chain gene (pTGHC9907) encoding a bovine IgG1 antibody against bovine herpes virus type 1 (BHV-1) isolated from a Holstein cow has led to the identification of a new IgG1 sequence allele. A comparison of nucleotide sequence of pTGHC9907 with the IgG1(a) (clone 2) and IgG1(b) (clone 8.10) sequence variants and unclassified IgG1 cDNA sequence (clone 8.75) has revealed significant differences in the hinge region spanning codons 216-230. The Thr224 and Thr226 of IgG1(a) were replaced with Arg224 and Pro226, while both Thr218 and Pro224 of IgG1(b) were substituted with Arg with deletion of Ser225 in HB9907 antibody. Additional amino acid substitutions were noted in the CH1 (positions 190, 192), CH2 (position 281) and CH3 (position 402) exons. Thus, the polymorphic sites occurred in all constant domains, but were clustered in the hinge region of IgG1. Examination of a three-dimensional model of the HB9907 heavy chain revealed that all sequence variations were on the surface of the IgG and are possible targets for recognition by antisera and effector molecules such as cellular adhesion molecules. The presence in the CH1 domain of a repeating motif of Pro-Ala-Ser-Ser indicated a potential structure-enhancing function and a role in cellular adhesion and migration. Replacement of Thr with Arg residues within the hinge was predicted to have a dual effect of reducing the number of O-linked glycosylation sites and increasing the susceptibility to degradation by protease-secreting bacteria of the hinge region. As unclassified IgG1 cDNA sequence (clone 8.75) is structurally distinct from other variants, it is also classified as IgG1(d). Collectively, these observations support the identification of a new allotypic variant of bovine IgG1, designated as IgG1(c) that is distinct in both sequence and structure from the known sequence variants.

show abstract

Section: Resultsmentioning

confidence: 85%

Structural Evidence for a New IgG1 Antibody Sequence Allele of Cattle

Saini¹,

Farrugia²,

Muthusamy³

et al. 2006

Scand J Immunol

View full text Add to dashboard Cite

show abstract

“…Many pathogens that colonize the mucosal surface, including Nm produce secreted IgA proteases that cleave IgA1 at hinge region and remove the Fc portion. It has been postulated that the remaining Fab fragments may bind or remain bound to the organism, however other studies have reported low affinity of the remaining Fab portion of IgA 228 . The precise biological significance of IgA protease remains elusive.…”

Section: Complement Evasion Strategies Used By Nmmentioning

confidence: 99%

Meningococcal disease and the complement system

Lewis¹,

2013

View full text Add to dashboard Cite

Despite considerable advances in the understanding of the pathogenesis of meningococcal disease, this infection remains a major cause of morbidity and mortality globally. The role of the complement system in innate immune defenses against invasive meningococcal disease is well established. Individuals deficient in components of the alternative and terminal complement pathways are highly predisposed to invasive, often recurrent meningococcal infections. Genome-wide analysis studies also point to a central role for complement in disease pathogenesis. Here we review the pathophysiologic events pertinent to the complement system that accompany meningococcal sepsis in humans. Meningococci use several often redundant mechanisms to evade killing by human complement. Capsular polysaccharide and lipooligosaccharide glycan composition play critical roles in complement evasion. Some of the newly described protein vaccine antigens interact with complement components and have sparked considerable research interest.

show abstract

“…However, the neutralizing activity mediated by the Fv domains of these antibodies has been found to be insufficient for their protective effects in numerous settings(Clynes et al, 2000; Johnson and Glennie, 2003; Schmidt and Gessner, 2005; Hessell et al, 2007), and evidence of the importance of the constant domain's effector function in clinical outcomes has been accumulating across fields ranging from cancer immunotherapy(Dall'Ozzo et al, 2004) to autoimmunity(Laszlo et al, 1986) and chronic viral infection(Shore et al, 1974). Analogously to the Fv escape mechanisms such as mutating surface epitopes, several pathogens evade the Fc-mediated antibody response by expressing proteases that restrict the Fc domain(Shakirova et al, 1985; Berasain et al, 2000; Collin et al, 2002; Vidarsson et al, 2005; Aslam et al, 2008), or glycosidases that remove the sugar residues required for interaction with Fc receptors(Allhorn et al, 2008). Combined, these evasion mechanisms and clinical correlates provide strong evidence as to the importance of Fc-based effector functions in the therapeutic activity of antibodies.…”

Section: Introductionmentioning

confidence: 99%

A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples

Ackerman

Moldt

Wyatt

et al. 2011

Journal of Immunological Methods

409

424

View full text Add to dashboard Cite

Phagocytosis can be induced via the engagement of Fcγ receptors by antibody-opsonized material. Furthermore, the efficiency of antibody-induced effector functions has been shown to be dramatically modulated by changes in antibody glycosylation. Because infection can modulate antibody glycans, which in turn modulate antibody functions, assays capable of determining the induction of effector functions rather than neutralization or titer provide a valuable opportunity to more fully characterize the quality of the adaptive immune response. Here we describe a robust and high-throughput flow cytometric assay to define the phagocytic activity of antigen-specific antibodies from clinical samples. This assay employs a monocytic cell line that expresses numerous Fc receptors: including inhibitory and activating, and high and low affinity receptorsallowing complex phenotypes to be studied. We demonstrate the adaptability of this highthroughput, flow-based assay to measure antigen-specific antibody-mediated phagocytosis against an array of viruses, including influenza, HIV, and dengue. The phagocytosis assay format further allows for simultaneous analysis of cytokine release, as well as determination of the role of specific Fcγ-receptor subtypes, making it a highly useful system for parsing differences in the ability of clinical and vaccine induced antibody samples to recruit this critical effector function.

show abstract

Working Mechanism of Immunoglobulin A1 (IgA1) Protease: Cleavage of IgA1 Antibody toNeisseria meningitidisPorA Requires De Novo Synthesis of IgA1 Protease

Cited by 23 publications

References 33 publications

Structural Evidence for a New IgG1 Antibody Sequence Allele of Cattle

Structural Evidence for a New IgG1 Antibody Sequence Allele of Cattle

Meningococcal disease and the complement system

A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples

Contact Info

Product

Resources

About