Ziyang Zhang, PhD
Reshaping iNKT Cell Response With Small Molecule Ligands of CD1d
Abstract
Natural killer T (NKT) cells are a group of T cells that rapidly produce cytokines and affect the immune system in many settings. Unlike conventional T cells, NKT cells respond to lipid-based antigens presented by the non-classical major histocompatibility complex protein CD1d. CD1d-mediated signaling to NKT cells has prominent roles in cancer and inflammatory diseases. While attractive as a therapeutic target, theapeutic modulation of CD1d signaling requires the ability to control of both the magnitude and balance between Th1 and Th2 responses of NKT cells. Here we propose to develop small molecule ligands of CD1d that bias or antagonize NKT cell responses to modulate the function NKT cells. In the 1-year grant period, we propose to 1) develop assays and perform screens identify small molecule ligands that bind in the A’ pocket of CD1d and 2) assess the effect of these ligands on NKT cell response to structurally diverse lipid antigens.
The support from the PhRMA Foundation allows us to test a new hypothesis in the infancy of my independent lab. The project will help us develop chemical tools to probe immune signaling, which could unlock new therapeutic mechanisms for autoimmune diseases.
