"Non-catalytic Tyrosine-phosphorylated Receptors (NTRs) on Leucocytes Play a Crucial Role in Immune Recognition"

P. Anton van der Merwe, PhD
Professor, Molecular Immunology
University of Oxford

White blood cells (leucocytes) continuously migrate throughout the body looking for microorganisms, infected cells, or cancer. They use cell surface receptors to detect and eliminate infection and cancer. The largest group of such receptors, which we term non-catalytic tyrosine phosphorylated receptors (NTRs), share key features including small size and the fact that their intracellular portions are phosphorylated on tyrosine residues when they bind extracellular ligands. We have proposed, and provided evidence to show, that NTRs transduce signals by a novel kinetic-segregation mechanism.

Many NTRs are inhibitory and bind molecules expressed on normal cells. Whether a white cell is activated depends on the balance between the number of activatory and inhibitory NTRs that are engaged when it interacts with another cell. We have shown that signal integration between these NTRs requires close colocalization, and have proposed that this membrane-proximal signal integration enables leukocytes to sensitively detect and selectively eliminate abnormal cells. NTRs often aggregate into clusters following ligand binding. We suggest that one reason for this clustering is to enhance discrimination between low and high affinity ligands.

Faculty host: Cheng Zhu, PhD