Bivalent Binding of IgA1 to FcαRI Suggests a Mechanism for Cytokine Activation of IgA Phagocytosis

Herr, Andrew B.; White, Clinton L; Milburn, Christina; Wu, Carol A.; Björkman, Pamela J.

doi:10.1016/s0022-2836(03)00149-9

Cited by 88 publications

(121 citation statements)

References 51 publications

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“…In the IgA system, there is the same agreement between the K a of 1. (29). Although another IgY-Fc receptor, ggFcR, has been described on chicken monocytes (11), in the FACS assay reported here, almost all IgY binding to cells was inhibited by an excess of smCHIR-AB1.…”

mentioning

confidence: 60%

“…(kinetic analysis). The K a values for the two sites differ by a factor of approximately six, whereas those for Fc␣RI binding to IgA-Fc, which also shows 2:1 stoichiometry, differ only by a factor of approximately two (29). In the crystal structure of the IgA-Fc-receptor complex, IgA-Fc has 2-fold rotational symmetry (13), and the two sites are therefore structurally identical.…”

Section: Discussionmentioning

confidence: 98%

“…An x-ray structure for the IgY-smCHIR-AB1 complex is clearly needed. Our previous finding that the C2 domains play little or no role in the kinetics of IgY binding to receptor (6), unlike the homologous C⑀2 domains in IgE (30) (29). Dephosphorylation of Fc␣RI by protein phosphatase 2A has now been identified as the activation switch for IgA bound to its receptor on neutrophils (31).…”

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confidence: 99%

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A Monomeric Chicken IgY Receptor Binds IgY with 2:1 Stoichiometry

Taylor

Beavil

Sutton

et al. 2009

Journal of Biological Chemistry

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Fc receptors link the specificity of the adaptive immune system with the effector mechanisms of innate immune cells. In birds and reptiles, IgY is the principal serum antibody, and both mammalian IgG and IgE have evolved from an IgY-like ancestor, so studies of IgY offer insights into their origins (1). The historical contribution of chicken immunology to a wider understanding of the subject has been considerable (2), and recently several chicken IgY-Fc receptors have been identified. In this paper, the chicken antibody, IgY, is shown to bind to a chicken leukocyte receptor, CHIR-AB1, 4 in a different manner from that of its mammalian orthologues, IgG and IgE, to their respective Fc receptors. Phagocytosis, mediated in mammals by IgG, and passive cutaneous anaphylaxis, mediated by both IgG and IgE in mammals, have been observed in chickens (3, 4), presumably both effected by IgY. In vitro, IgY binds to monocyte cell lines (5, 6), and an IgY receptor (CHIR-AB1) has been identified that is able to mediate the influx of calcium into cells (5).The genes for the mammalian high affinity IgE receptor, and several IgG receptors, are located in the classical Fc receptor cluster, whereas in chickens, this cluster is represented by a single gene, the product of which has been expressed and found not to bind IgY (7). Intriguingly, the first IgY leukocyte receptor, CHIR-AB1, was found to be a member of the chicken leukocyte receptor cluster (LRC) (5), adjacent to over 100 genes with high intersequence homology (8). This finding, together with phylogenetic analysis of the orthologous Fc receptor gene clusters (7, 9), implies that during the evolution of the IgY-like ancestor of both IgG and IgE, antibody-Fc binding function migrated from proteins expressed in the LRC to those in the classical Fc receptor cluster. The human LRC is the site of Fc␣RI, the leukocyte receptor for IgA (an antibody involved in mucosal immunity), the fetal IgG receptor (FcRn, involved in adult IgG homeostasis), and also a number of natural killer cell receptors including the HLA-G ligand, KIR2DL4 (10). A further leukocyte receptor for chicken IgY, also related to LRC receptors, was identified recently, on chromosome 20 (11), and remains to be characterized.Typically, the stoichiometry of the receptor-antibody complex differs for receptors located in the classical Fc receptor cluster and the LRC. Crystal structures of IgG complexes with Fc␥RIII and of IgE with Fc⑀RI show 1:1 receptor:antibody stoichiometry, with the receptor binding across both heavy chains in the lower hinge (12). In contrast, the crystal structure of Fc␣RI complexed with IgA shows 2:1 stoichiometry (13)

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confidence: 60%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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A Monomeric Chicken IgY Receptor Binds IgY with 2:1 Stoichiometry

Taylor

Beavil

Sutton

et al. 2009

Journal of Biological Chemistry

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“…The weight-averaged reduced buoyant molecular weight, w, was determined followed by analysis of the monomerdimer equilibrium. Calculation of the experimental molecular weights from , determination of the monomer-dimer equilibrium constants, and conversion of equilibrium constants into molar units were carried out as described (35,36). Complete experimental procedures are described in SI Text.…”

Section: Methodsmentioning

confidence: 99%

A zinc-dependent adhesion module is responsible for intercellular adhesion in staphylococcal biofilms

Conrady

Brescia

Horii

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

194

285

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Hospital-acquired bacterial infections are an increasingly important cause of morbidity and mortality worldwide. Staphylococcal species are responsible for the majority of hospital-acquired infections, which are often complicated by the ability of staphylococci to grow as biofilms. Biofilm formation by Staphylococcus epidermidis and Staphylococcus aureus requires cell-surface proteins (Aap and SasG) containing sequence repeats known as G5 domains; however, the precise role of these proteins in biofilm formation is unclear. We show here, using analytical ultracentrifugation (AUC) and circular dichroism (CD), that G5 domains from Aap are zinc (Zn 2؉ )-dependent adhesion modules analogous to mammalian cadherin domains. The G5 domain dimerizes in the presence of Zn 2؉ , incorporating 2-3 Zn 2؉ ions in the dimer interface. Tandem G5 domains associate in a modular fashion, suggesting a ''zinc zipper'' mechanism for G5 domain-based intercellular adhesion in staphylococcal biofilms. We demonstrate, using a biofilm plate assay, that Zn 2؉ chelation specifically prevents biofilm formation by S. epidermidis and methicillin-resistant S. aureus (MRSA). Furthermore, individual soluble G5 domains inhibit biofilm formation in a dose-dependent manner. Thus, the complex threedimensional architecture of staphylococcal biofilms results from the self-association of a single type of protein domain. Surface proteins with tandem G5 domains are also found in other bacterial species, suggesting that this mechanism for intercellular adhesion in biofilms may be conserved among staphylococci and other Gram-positive bacteria. Zn 2؉ chelation represents a potential therapeutic approach for combating biofilm growth in a wide range of bacterial biofilm-related infections.bacterial pathogenesis ͉ G5 domain ͉ Aap ͉ chelation ͉ Staphylococcus

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“…IgG receptor Fc␥RIII and IgE receptor Fc⑀RI bind antibodies in the near hinge regions and form 1:1 complexes (8,9), whereas Fc␣RI binds the C H 2-C H 3 interface of Fc␣ (10,11) and preferably forms 2:1 complex with a single Fc␣ homodimer (12). It has been reported that Fc␥Rs and Fc⑀RI use their membrane proximal-domain and linker region binds immunoglobulin (8,9,13,14), whereas Fc␣RI uses its membrane-distal domain EC1 to bind IgA (15).…”

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confidence: 99%

Crystal Structure of the Ectodomain of Human FcαRI

Ding

Yang

et al. 2003

Journal of Biological Chemistry

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Human Fc␣RI (CD89) is the receptor specific for IgA, an immunoglobulin that is abundant in mucosa and is also found in high concentrations in serum. Although Fc␣RI is an immunoglobulin Fc receptor (FcR), it differs in many ways from FcRs for other immunoglobulin classes. The genes of most FcRs are located on chromosome 1 at 1q21-23, whereas Fc␣RI is on chromosome 19, at 19q13.4, a region called the leukocyte receptor complex, because it is clustered with several leukocyte receptor families including killer cell inhibitory receptors (KIRs) and leukocyte Ig-like receptors (LIRs). The amino acid sequence of Fc␣RI shares only 20% homology with other FcRs but it has around 35% homology with its neighboring LIRs and KIRs. In this work, we analyzed the crystal structure of the ectodomain of Fc␣RI and examined structure similarities between Fc␣RI and KIR2DL1, KIR2DL2 and LIR-1. Our data show that Fc␣RI, KIRs, and LIRs share a common hydrophobic core in their interdomain interface, and Fc␣RI is evolutionally closer to LIR than KIR.In humans, IgA is the most abundant immunoglobulin in secretions, and it constitutes about 20% of the immunoglobulin pool in serum (1, 2). Since its turnover rate is faster than other immunoglobulins, the daily production of IgA exceeds all other immunoglobulins combined (3). Undoubtedly, IgA should to play important roles in immune defense against invaded pathogens.Five types of IgA receptors have been recognized so far. They are Fc␣RI (CD89), the polymeric Ig receptor, Fc␣/R, the transferrin receptor, and the asialoglycoprotein receptor (1). Among them, Fc␣RI is the only one that specifically binds IgA. On ligation of IgA complexed with antigens, Fc␣RI is able to mediate various cellular responses including phagocytosis, antibody-dependent cell cytotoxicity, oxidative bursts, and release of inflammatory mediators (1).Fc␣RI belongs to the immunoglobulin superfamily and contains an extracellular region of 206 amino acids, a transmembrane domain of 19 amino acids and a cytoplasmic region of 41 amino acids (4 Although Fc␣RI is an immunoglobulin Fc receptor (FcR), 1 it differs in many ways with FcRs for other immunoglobulin classes. IgG receptor Fc␥RIII and IgE receptor Fc⑀RI bind antibodies in the near hinge regions and form 1:1 complexes (8, 9), whereas Fc␣RI binds the C H 2-C H 3 interface of Fc␣ (10, 11) and preferably forms 2:1 complex with a single Fc␣ homodimer (12). It has been reported that Fc␥Rs and Fc⑀RI use their membrane proximal-domain and linker region binds immunoglobulin (8, 9, 13, 14), whereas Fc␣RI uses its membrane-distal domain EC1 to bind IgA (15).The genes of most FcRs are located in chromosome 1 at 1q21-23 (16), whereas Fc␣RI is in chromosome 19, at 19q13.4 (17, 18), a region called the leukocyte receptor complex because it is clustered with several leukocyte receptor families including killer cell inhibitory receptors (KIRs) and leukocyte Ig-like receptors (LIR/LILR/ILTs) (17, 18). The amino acid sequence of Fc␣RI shares only 20% homology with other FcRs, but it has around...

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Bivalent Binding of IgA1 to FcαRI Suggests a Mechanism for Cytokine Activation of IgA Phagocytosis

Cited by 88 publications

References 51 publications

A Monomeric Chicken IgY Receptor Binds IgY with 2:1 Stoichiometry

A Monomeric Chicken IgY Receptor Binds IgY with 2:1 Stoichiometry

A zinc-dependent adhesion module is responsible for intercellular adhesion in staphylococcal biofilms

Crystal Structure of the Ectodomain of Human FcαRI

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