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

Abstract

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)

Amino acid substitution in the Cυ3 domain causes either elevation or reduction of IgY uptake into egg yolks of quail

“…The tyrosine residue at position 363 is highly conserved among amphibian, reptile, and avian species (Taylor et al, 2010). The X-ray crystallographic structure of the IgY-Fc fragment of chicken showed that PEGLY at positions 359-363 forms the ␣-helix followed by the turn and bend structure at the C-terminal, which are located in an exposed loop in close proximity to another loop of the C 4 domain (Taylor et al, 2009). Thus, it seems likely that the aromatic side chain at Y363 directly or indirectly contributes to an interaction with an unidentified IgY receptor for egg yolk transport.…”

“…This result suggests that the N408 carbohydrate chain plays a more critical role in IgY uptake into egg yolks than does the N308 carbohydrate chain. The N408 carbohydrate chain is located near the C 3/C 4 interface in the 3D structure (Taylor et al, 2009), so that deletion of the N408 carbohydrate chain may influence the conformation of IgY-Fc, and perhaps result in extremely lowered IgY-Fc uptake into egg yolks. Another finding of the present study is that the absence of either the N308 carbohydrate chain or N408 carbohydrate chain reduced blood IgY-Fc concentrations to nearly the same extent.…”

“…It was later shown that the synthesized recombinant cIgY-Fc had the potential to interact with two IgY-Fc receptors, CHIR-AB1 and ggFcR (Taylor et al, 2009;Schreiner et al, 2012). We also synthesized cIgY-Fc mainly consisting of C 3 and C 4 domains, and the critical amino acid residues contributing to efficient IgY transport into egg yolks were investigated in vivo by using Japanese quail (Coturnix japonica), since its small body size and excellent egg productivity are advantageous for IgY fate-tracing experiment.…”

Fc Receptors in Mucosal Immunology

“…The chicken receptor CHIR-AB1, encoded by a gene lying within the chicken LRC, binds to a position on its ligand IgY equivalent to that bound by FcαRI on IgA. The chicken IgY-CHIR-AB1 interaction also shares the 2:1 ligand:receptor stoichiometry (Purzel et al, 2009;Taylor et al, 2009Taylor et al, , 2010. The evolutionary implications are that a major shift occurred in the mode of Fc receptor binding during the evolution of mammalian IgG and IgE, such that there was a migration away from receptor recognition of the Fc interdomain region (exemplified by the Cα2/Cα3 interface in IgA) to a site in the N-terminal region of the Cγ2/ Cε3 domain.…”

Structure analysis of goose immunoglobulin Y Fc fragment

“…Immunoglobulin Y (IgY) is the principal serum antibody in birds and reptiles, and an IgY-like molecule was the evolutionary precursor of both mammalian IgG and IgE [1]. The IgY heavy chain consists of four constant domains, and the Fc fragment mainly contains two constant domains on the C-terminal, the Cυ3 domain and the Cυ4 domain [2,3].…”