University of California, San Francisco
Principal Investigator: Dr. Scott Zamvil
Project Title: Aquaporin 4 (AQP4) Specific T Cells in
Autoantibodies directed against aquaporin 4 (AQP4), the primary candidate autoantigen in neuromyelitis optica (NMO), are detected in a high percentage of NMO patients. These AQP4-specific antibodies are IgG1, a subclass of mature IgG that requires help from CD4+ T cells. However, little is known regarding the T cells that react to AQP4. To further understand the role of AQP4 in NMO, it is critical to characterize how T cells recognize this protein. The Zamvil Lab hypothesizes that AQP4-specific T cells may be activated and/or expanded in NMO patients. In this research program, they will identify and characterize the determinants of AQP4 that are recognized by T cells in NMO patients using cells derived from blood samples. In addition, an animal model of NMO would be advantageous for understanding certain pathogenic features and for the development and preclinical testing of candidate therapies. They propose to characterize T cells from mice that recognize AQP4 and develop a murine model of NMO that more closely resembles the human disease than those that currently exist. The approach is to identify pathogenic determinants of AQP4 using fragments encompassing the entire sequence of AQP4, as well as the intact AQP4 molecule. Identification of these T cells in humans and mice should also provide insight regarding the development of the humoral (antibody) AQP4-specific response, and may identify new targets for therapeutic intervention.
UCSF, Zamvil Lab Team