TY - JOUR
T1 - Evidence for carbohydrate recognition and homotypic and heterotypic binding by the TIM family
AU - Wilker, Peter R.
AU - Sedy, John R.
AU - Grigura, Vadim
AU - Murphy, Theresa L.
AU - Murphy, Kenneth M.
N1 - Funding Information:
The glycan array analysis was conducted by the Protein–Carbohydrate Interaction Core of The Consortium for Functional Glycomics funded by the National Institute of General Medical Sciences grant GM62116. We thank Richard Alvarez, Director Core H, for helpful advice and assistance. We also thank D. Fremont and C. Nelson for help with protein production. This work was supported by the Howard Hughes Medical Institute (K.M.M.) and the National Institutes of Health (NIH 5 PO1 AI031238).
PY - 2007/6
Y1 - 2007/6
N2 - The T cell Ig domain and mucin domain (TIM) proteins form a conserved family of transmembrane cell-surface glycoproteins expressed by a variety of tissues. Each TIM protein contains a single V-type Ig domain, a glycosylated mucin-like domain, a transmembrane domain and a cytoplasmic domain. TIM proteins recognize a diverse array of ligands, including H-ferritin, galectin-9 as well as other TIM family members. In this study, we demonstrate that the Ig domains of murine TIM-1, -3 and -4 display calcium-dependent binding to ligands expressed by murine splenocytes and several non-murine cell lines, indicating non-species-specific ligand recognition. Further, the intrafamilial interaction of various TIM family Ig domains with surface-expressed TIM-1 and TIM-4 requires an intact TIM-1 and TIM-4 glycosylated mucin stalk. Importantly, we also uncovered the previously unrecognized potential for homotypic TIM interactions in forming ligand-receptor pairs. Using a glycan array screen, we identified the novel capacity of the TIM-3 Ig domain to recognize specific carbohydrate moieties, suggesting a role for carbohydrate modification along with protein epitopes in TIM ligand recognition. Identification of the carbohydrate-binding capacity of TIM proteins helps explain the diversity of ligands recognized by this family and adds to our understanding of homotypic and heterotypic interactions between TIM family members.
AB - The T cell Ig domain and mucin domain (TIM) proteins form a conserved family of transmembrane cell-surface glycoproteins expressed by a variety of tissues. Each TIM protein contains a single V-type Ig domain, a glycosylated mucin-like domain, a transmembrane domain and a cytoplasmic domain. TIM proteins recognize a diverse array of ligands, including H-ferritin, galectin-9 as well as other TIM family members. In this study, we demonstrate that the Ig domains of murine TIM-1, -3 and -4 display calcium-dependent binding to ligands expressed by murine splenocytes and several non-murine cell lines, indicating non-species-specific ligand recognition. Further, the intrafamilial interaction of various TIM family Ig domains with surface-expressed TIM-1 and TIM-4 requires an intact TIM-1 and TIM-4 glycosylated mucin stalk. Importantly, we also uncovered the previously unrecognized potential for homotypic TIM interactions in forming ligand-receptor pairs. Using a glycan array screen, we identified the novel capacity of the TIM-3 Ig domain to recognize specific carbohydrate moieties, suggesting a role for carbohydrate modification along with protein epitopes in TIM ligand recognition. Identification of the carbohydrate-binding capacity of TIM proteins helps explain the diversity of ligands recognized by this family and adds to our understanding of homotypic and heterotypic interactions between TIM family members.
KW - Ligands
KW - T lymphocytes
KW - Tetramers
UR - http://www.scopus.com/inward/record.url?scp=34447576949&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxm044
DO - 10.1093/intimm/dxm044
M3 - Article
C2 - 17513880
AN - SCOPUS:34447576949
SN - 0953-8178
VL - 19
SP - 763
EP - 773
JO - International Immunology
JF - International Immunology
IS - 6
ER -