TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis.
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.
Chen
Thomas T
TT
Veterans Administration Medical Center, San Francisco, CA 94121, USA.
Li
Li
L
Chung
Dong-Hui
DH
Allen
Christopher D C
CD
Torti
Suzy V
SV
Torti
Frank M
FM
Cyster
Jason G
JG
Chen
Chih-Ying
CY
Brodsky
Frances M
FM
Niemi
Eréne C
EC
Nakamura
Mary C
MC
Seaman
William E
WE
Daws
Michael R
MR
D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D017931:DNA Primers; D004705:Endocytosis / Q000276:immunology*; D005293:Ferritins / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D008565:Membrane Proteins; C442242:Timd2 protein, mouse; D049452:Green Fluorescent Proteins; D005293:Ferritins