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Research Division Faculty


 
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Niyun Jin, MD
Primary Appointment: Instructor, Pediatrics
 

Our research focuses
 on roles of pathogenic CD4 T cells in the development of Type 1 diabetes(T1D) and how major histocompatibility (MHC) class II recognize antigenic peptides. We are also interested in preventing type 1 diabetes in nonobese diabetic (NOD) mice by vaccination with Chromogranin A mimetope.
Type 1 diabetes is an autoimmune disease in which the insulin-producing beta cells with the islets of Langerhans of the pancreas are destroyed by T cell-mediated immune attack. Chromogranin A (ChgA) is an autoantigen for CD4+ T cells in the NOD mouse model of type 1 diabetes. The natural ChgA-processed peptide, WE14, is a weak agonist for the prototypical T cell, BDC-2.5, as well as a set of new ChgA-specific T-cell clones our lab discovered. 
It is predicted that the first five amino acids from WE14 (WSRMD) lie in the p5-p9 position in the mouse MHC class II, IAg7 binding groove. To increase stability of binding, we added amino acid RLGL to N-terminal of WE-14. RLGL-WE14 becomes much more potent than WE14 in T-cell stimulation and activation. The crystal structure of the IAg7–RLGL–WE14 complex solved in collaboration with Dr. Shaodong Dai’s laboratory confirms the predicted placement of the peptide within the IAg7 groove. We also studied different N-terminal amino acid extension to the WE14, the result showed that many of these extended peptides are sufficient to greatly improve T-cell stimulation. This result leads us to propose that a posttranslational modification may occur uniquely in the pancreas or pancreatic lymph nodes, perhaps via the mechanism of transpeptidation. This modification could account for the escape of these T cells from thymic negative selection.
It is known vaccination of an insulin mimetope can prevent Type 1 diabetes in NOD mouse model by converting naïve T cells into Foxp3+ regulatory T cells. We have vaccinated NOD mice with a Chromogranin A mimetope, the result showed that the vaccination could at least partially prevent Type 1 diabetes in NOD mice. Further investigation for this project is current underway.

 
Education:
MD: Wenzhou Medical College, Wenzhou, P.R. China

Please direct inquiries to specific e-mail addresses listed within individual entries. For all other general Research inquiries, please contact: 
Kathryn Gray, BFA, MA​​