Li Zhang, MD, PhD
Instructor, Department of Pediatrics, Barbara Davis Center
I believe the trimolecular (MHC II-autoantigen-TCR) is critical in the development of autoimmune disease. I investigated the insulin reactive T cell receptor repertoire aimed to explore the role of beta chain usage of pathogenic T cell receptors. I also discovered insulin B:9-23 responsive gamma/delta cells in NOD mouse. Collaborating with Dr. John Kappler group, I have discovered that insulin B:9-23 actually is presented in the register 3. Subsequently I have developed a therapeutic way to prevented diabetes successfully with an immunization of specific antigen-MHC complex with peptide fixed in register 3. My most recent research has focused on developing an antigen based therapeutic monoclonal antibody to prevent and stop the autoimmune progression of beta cell destruction by disturbing the process of autoantigen presentation relying on structural knowledge of how peptides are presented. Such a register 3 monoclonal antibody inhibits insulin responsive T cells in vitro and the development of insulitis in vivo by on-going data. We are trying to modify it to a drug usable therapeutic monoclonal antibody for T1D. It is promising to expand the same antigen based therapy principle to other autoimmune diseases and translate it to clinic in the future.
- Zhang L, Stadinski, B D, Michels A, John W. Kappler, Eisenbarth, G S. Immunization with an insulin peptide –MHC complex to prevent type 1 diabetes of NOD mice. Diabetes/Metabolism; Research and Reviews. 2011; 27(8):784-9
- Stadinski, B D, Zhang L, Crawford, F, Marrack, P, Eisenbarth, G S,and John W Kappler 2010 Diabetogenic T cells Recognize Insulin Bound to IAg7 in an Unexpected, Weakly Binding Register. PNAS. 2010 15; 107(24): 10978-83.
- Zhang L, Jasinski JM, Kobayashi M, Davenport B, Johnson K, Davidson H, Nakayama M, Haskins K, Eisenbarth GS. Analysis of T cell receptor beta chains that combine with dominant conserved TRAV5D-4*04 anti-insulin B:9-23 alpha chains. J Autoimmun. 2009 Aug; 33(1):42-9.
- Zhang, L., Niyun Jin, J M Wands, Maki Nakayama, Willi Born, George Eisenbarth. Gamma Delta Cells Recognizing the B:9-23 Peptide of NOD Mice. Clin. Immunol. 131:s74, 2009.
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