Table 2.
IgA receptors identified in humans and their function.
| Receptor | Recognition Site (Ig Type, Form) | Cell Type Expressing the Receptor | Function | Ref |
|---|---|---|---|---|
| pIgR | J-chain (pIgA, pIgM) |
Secretory epithelial cells in the intestine, salivary glands, bronchial mucosa, mammary glands, uterine | Transport of pIgA from lamina propria across the epithelial cells to secretions lumen, where it is released as SIgA (part of the receptor becomes part of SIgA; secretory component) | [30] |
| Epithelial cells of biliary duct | Transport of serum pIgA into the bile (which excretes into intestinal lumen) | |||
| DC-SIGN |
N-/O-linked glycans (SIgA) |
Dendritic cell Cell culture |
Binding and internalizing SIgA | [31] |
| Dectin-1 Siglec-5 | Cα1 and Cα2 (SIgA) |
M cell | IgA-specific receptor on the apical surface that mediates the transepithelial transport to GALT | [28,32] |
| ASGPR |
O-linked glycans on hinge region - terminal Gal or GalNAc of desialylated O-glycoproteins (free IgA1) |
Hepatocytes | Clearance of IgA1 from the circulation and catabolic degradation (lysosomal catabolism) | [12,23,33,34] |
| Monocytes | A mobile pool of the receptors, capable of reaching sites remote from the liver | |||
| Soluble form in circulation | Bind to free IgA1 in the circulation and transport to liver for uptake and degradation by hepatocytes [34] | |||
| TfR TfR1 (CD71) |
(IgA1; Monomeric better than polymeric) | Mesangial cells CD71 is expressed on a wide range of tissues TfR2 predominantly in the liver |
Clearance of IgA from the circulation Binding of IgA1 to TfR1 depends on the size and glycosylation of IgA1 and can be inhibited by transferring |
[24] |
| β-GalT1 | Fc region | Mesangial cells | Clearance of IgA from the circulation | [25] |
| Leukocyte receptors | ||||
| SCR | Secretory component (SIgA, SC) |
Eosinophils basophils | Generate respiratory burst and eosinophil degranulation, target killing, and release of proinflammatory cytokines and other mediators | [27,35] |
| FcRL4 | Fc region (IgA) |
Memory B cells in mucosal lymphoid tissue | Immune complex-dependent B cell regulation | [29] |
| Fcα/μR (CD351) | Fc region (IgA, IgM; Polymeric and immune complexes) |
Mature B cells, macrophages Constitutively express |
Endocytosis of IgA/IgM-coated microbes, phagocytosis higher affinity for IgM than IgA (10x) | [26] |
| FcαRI (CD89) | Fc region; CHα2 and CHα3, (immune complexes and pIgA better than monomeric SIgA only with lectin Mac-1) |
Neutrophils, eosinophils, monocytes, Kupffer cells, macrophages, subpopulation of T and B cells, subset of DC, NK | Bifunctional receptor – the function depends on IgA ligand avidity: Anti-inflammatory: (free mIgA) inhibition of phagocytic activity, stimulate release of anti-inflammatory cytokines by myeloid cells Proinflammatory: (IgA + Ag complex receptor cross-linking): stimulation of phagocytosis, respiratory burst, release of ROS and proinflammatory cytokines, antigen presentation, antibody-dependent cellular cytotoxicity |
[36,37] |
| Soluble form of CD89 in circulation | Binds CD71 and induces TGase 2, which in turn is translocated to the mesangial plasma membrane allowing cell activation by IgA1-sCD89 complexes | |||
LEGEND: pIgR: polymeric immunoglobulin receptor; β-GalT1: β-1,4-galactosyltransferase1; ASGPR: asialoglycoprotein receptor; FcRL4: Fc receptor-like 4; TfR: transferrin receptor (CD71); SCR: secretory component receptor; FcαRI: Fc alpha receptor 1; GalNAc: N-acetylgalactosamine; GALT: gut associated lymphoid tissue; FcRL: Fc receptor-like.