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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-01-0076.
Submitted January 10, 2002
Accepted June 18, 2002
Structural, functional, and tissue distribution analysis of human transferrin receptor-2 by murine monoclonal antibodies and a polyclonal antiserum
Silvia Deaglio, Andrea Capobianco, Angelita Cali, Francesca Bellora, Federica Alberti, Luisella Righi, Anna Sapino, Clara Camaschella, and Fabio Malavasi*
Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Turin Medical School, Turin, Italy; Experimental Medicine Research Center, University of Turin Medical School, Turin, Italy
Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Turin Medical School, Turin, Italy
Department of Clinical and Biological Sciences, University of Turin Medical School, Turin, Italy
Department of Biomedical Sciences and Human Oncology, University of Turin Medical School, Turin, Italy
* Corresponding author; email: fabio.malavasi{at}unito.it.
Human transferrin receptor-2 (TFR-2) is a protein highly homologous to TFR-1/CD71 and endowed with the ability to bind transferrin (TF) with low affinity. High levels of TFR-2 mRNA were found in the liver and in erythroid precursors. Mutations affecting TFR-2 gene lead to hemochromatosis type 3, a form of inherited iron overload. Several issues on distribution and function of the receptor were answered by raising a panel of 9 mAbs specific for TFR-2 by immunizing mice with murine fibroblasts transfected with the human TFR-2 cDNA. A polyclonal antiserum was also produced in mice immunized with 3 peptides derived from the TFR-2 sequence, exploiting an innovative technique. The specificity of all the reagents produced was confirmed by the reactivity with TFR-2+ target cells and simultaneous negativity with TFR-1+ cells. Western blot analyses showed a dominant chain of ~90 kD in TFR-2 transfectants and HepG2 cell line. Analysis of distribution in normal tissues as well as representative cell lines revealed that TFR-2 displays a restricted expression pattern, being present at high levels in hepatocytes and in the epithelial cells of the small intestine, including the duodenal crypts. Exposure of human TFR-2+ cells to transferrin-bound iron is followed by a significant up-regulation and re-localization of membrane TFR-2. The tissue distribution pattern, the behavior following exposure to iron-loaded TF and the features of the disease resulting by TFR-2 inactivation support the hypothesis that TFR-2 contributes to body iron sensing.
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