Structure and function of the activating receptor CLEC-2. (134.10)

• Published in: The Journal of immunology (1950) Vol. 182; no. 1_Supplement; pp. 134 - 134.10
• Main Authors: O'Callaghan, Chris A, Watson, Aleksandra A, Fenton-May, Angharad E, Christou, Charita M
• Format: Journal Article
• Language: English
• Published: 01.04.2009
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.134.10

We are studying the immune recognition of diseased or damaged cells. In cytotoxic cells, the C-type lectin-like receptor NKG2D plays a key role in this distinction. A number of related receptors are expressed on immune cells and we are studying their function. CLEC-2 is an activating receptor which is also expressed on platelets. We have crystallized CLEC-2 and solved its structure. We have used recombinant CLEC-2 as a probe to identify an endogenous ligand for CLEC-2, which is known as podoplanin. The podoplanin-CLEC-2 interaction triggers an activating signal in the cell expressing CLEC-2. We have also solved the crystal structure of rhodocytin, an exogenous ligand for CLEC-2. The structures of both ligand and receptor allow us to produce molecular models of the interactions and its effects. These suggest that the ligand-receptor interactions will cluster CLEC-2 on the cell surface. We have used surface plasmon resonance to define the binding characteristics of the interactions of CLEC-2 with both its exogenous and endogenous ligands.