Identification of the Transferrin Receptor as a Novel Immunoglobulin (Ig)a1 Receptor and Its Enhanced Expression on Mesangial Cells in Iga Nephropathy

Abstract

The biological functions of immunoglobulin (Ig)A antibodies depend primarily on their interaction with cell surface receptors. Four IgA receptors are presently characterized. The FcαRI (CD89) expressed by myeloid cells selectively binds IgA1 and IgA2 antibodies, whereas the poly-IgR, Fcα/μR, and asialoglycoprotein receptors bind other ligands in addition to IgA. IgA binding by mesangial cells, epithelial cells, and proliferating lymphocytes is also well documented, but the nature of the IgA receptors on these cells remains elusive. A monoclonal antibody (A24) is described here that specifically blocks IgA binding to epithelial and B lymphocyte cell lines. Both the A24 antibody and IgA1 myelomas bind a cell surface protein that is identified as the transferrin receptor (CD71). The transferrin receptor selectively binds IgA1 antibodies, monomeric better than polymeric forms, and the IgA1 binding is inhibitable by transferrin. Transferrin receptor expression is upregulated on cultured mesangial cells as well as on glomerular mesangial cells in patients with IgA nephropathy. The characterization of transferrin receptor as a novel IgA1 receptor on renal mesangial cells suggests its potential involvement in the pathogenesis of IgA nephropathy.

A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients

“…Anti-CD25-fluorescein isothiocyanate (FITC), anti-CD3-allophycocyanin (APC), anti-TfR-phycoerythrin (PE), irrelevant mouse IgG-FITC, mouse IgG-APC, and mouse IgG-PE isotype controls were all from Immunotech (Marseille, France). Chemotherapeutic agents were used at the following concentrations: zidovudine (AZT; Wellcome Research Labs, Beckenham, United Kingdom) at 0.2 M, anti-IL-2R␣ mAb (Hoffmann-La Roche, Nutley, NJ) at 10 g/mL, IFN-␣ (Hoffman-La Roche, Basel, Switzerland) at 100 U/mL, and arsenic trioxide (Sigma Chemical, St Louis, MO) at 1 M. The anti-human TfR (CD71) mAb A24 has been already described in detail 26 and the isotype-matched mAb 30.9 directed against the rat Fc⑀RI chain was used as a control. 27 Protein concentrations were determined using the BCA kit as recommended by the manufacturer (Pierce, Rockford, IL).…”

“…26 Because TfR expression is required for T-cell growth, we tested ANTI-TfR (mAb A24) IMMUNOTHERAPY AGAINST ATL CELLS 1839…”

“…[23][24][25] It has been shown that neutralizing anti-TfR antibodies can block the interaction between transferrin and TfR, and consequently iron uptake, leading to iron deprivation and negative regulation of cell growth. In this work, we have investigated the level of expression of TfR in tumor cells from acute and chronic ATL forms and the in vitro impact of a new neutralizing anti-TfR monoclonal antibody (mAb), A24, 26 on cell proliferation and survival. We show that TfR is expressed on ATL lymphocytes, both in acute and chronic ATL forms.…”

Gluten induces coeliac-like disease in sensitised mice involving IgA, CD71 and transglutaminase 2 interactions that are prevented by probiotics

“…Intact gliadin 33-mer or p31-49 peptides complexed with IgA are retrotranscytosed via the transferrin receptor (CD71/ TfR1), an IgA receptor, which is overexpressed on the apical side of intestine epithelial cells in CD patients. 3,4 However, the factor promoting this overexpression is still unknown. The retrotranscytosis of IgA-gliadin complexes may trigger both innate and adaptive immune responses, which initiate CD enteropathy.…”

Dysfunctions of the Iga system: a common link between intestinal and renal diseases

“…2 The two alternative IgA receptors are the asialoglycoprotein receptor, expressed on hepatocytes, which recognizes terminal Gal residues on serum glycoproteins (including IgA) and conveys bound ligand for intracellular degradation, and the transferrin receptor (TfR), which selectively binds pIgA1 and is highly expressed on renal mesangial cells. 34 Of these IgA receptors, the FcaRI plays an essential anti-inflammatory role in immunity allowing the transmission of inhibitory signals following binding of mIgA. FcaRI is expressed on cells of the myeloid lineage including: neutrophils; monocytes; tonsillar, splenic, and alveolar macrophages and Kupffer cells; eosinophils; and subpopulations of dendritic cells.…”