Abstract
The T cell immunoglobulin mucin (Tim) family of receptors regulates effector CD4+ T cell functions and is implicated in autoimmune and allergic diseases. Tim-3 induces immunological tolerance, and engagement of the Tim-3 immunoglobulin variable (IgV) domain by galectin-9 is important for appropriate termination of T helper 1-immune responses. The 2 Å crystal structure of the Tim-3 IgV domain demonstrated that four cysteines, which are invariant within the Tim family, form two noncanonical disulfide bonds, resulting in a surface not present in other immunoglobulin superfamily members. Biochemical and biophysical studies demonstrated that this unique structural feature mediates a previously unidentified galectin-9-independent binding process and suggested that this structural feature is conserved within the entire Tim family. The current work provided a graphic example of the relationship between sequence, structure, and function and suggested that the interplay between multiple Tim-3-binding activities contributes to the regulated assembly of signaling complexes required for effective Th1-mediated immunity.
Original language | English (US) |
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Pages (from-to) | 311-321 |
Number of pages | 11 |
Journal | Immunity |
Volume | 26 |
Issue number | 3 |
DOIs | |
State | Published - Mar 23 2007 |
Keywords
- HUMDISEASE
- MOLIMMUNO
- SIGNALING
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases