TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis

J Exp Med. 2005 Oct 3;202(7):955-65. doi: 10.1084/jem.20042433.

Abstract

T cell immunoglobulin-domain and mucin-domain (TIM) proteins constitute a receptor family that was identified first on kidney and liver cells; recently it was also shown to be expressed on T cells. TIM-1 and -3 receptors denote different subsets of T cells and have distinct regulatory effects on T cell function. Ferritin is a spherical protein complex that is formed by 24 subunits of H- and L-ferritin. Ferritin stores iron atoms intracellularly, but it also circulates. H-ferritin, but not L-ferritin, shows saturable binding to subsets of human T and B cells, and its expression is increased in response to inflammation. We demonstrate that mouse TIM-2 is expressed on all splenic B cells, with increased levels on germinal center B cells. TIM-2 also is expressed in the liver, especially in bile duct epithelial cells, and in renal tubule cells. We further demonstrate that TIM-2 is a receptor for H-ferritin, but not for L-ferritin, and expression of TIM-2 permits the cellular uptake of H-ferritin into endosomes. This is the first identification of a receptor for ferritin and reveals a new role for TIM-2.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • B-Lymphocytes / metabolism*
  • Cell Line, Tumor
  • Cloning, Molecular
  • DNA Primers
  • Endocytosis / immunology*
  • Ferritins / metabolism*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Green Fluorescent Proteins
  • Immunohistochemistry
  • Kidney / metabolism*
  • Liver / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Polymerase Chain Reaction

Substances

  • Antibodies, Monoclonal
  • DNA Primers
  • Membrane Proteins
  • Timd2 protein, mouse
  • Green Fluorescent Proteins
  • Ferritins