Evidence for carbohydrate recognition and homotypic and heterotypic binding by the TIM family.

Abstract:

: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.

journal_name

Int Immunol

journal_title

International immunology

authors

Wilker PR,Sedy JR,Grigura V,Murphy TL,Murphy KM

doi

10.1093/intimm/dxm044

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

763-73

issue

6

eissn

0953-8178

issn

1460-2377

pii

dxm044

journal_volume

19

pub_type

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