基于胰岛素的i型糖尿病负调肽疫苗的分析-analysis of insulin-based negative peptide vaccine for type i diabetes mellitus.docxVIP

Investigation of Antagonist peptide vaccine based on insulin in Type 1 diabetesAbstractType 1 Diabetes (T1D) is an autoimmune disease characterized by T-cell–mediated elimination of insulin-producing pancreatic islet β-cells in both humans and nonobese diabetic (NOD) mice. Cytotoxic CD8+ T lymphocyte (CTL), reactive to β cell antigens, are required for T1D development in the NOD mouse model of the disease, and CD8+ T cells specific for β cell antigens can be detected in the peripheral blood of T1D patients.Antigen-specific immunotherapy is expected to be an ideal strategy for treating T1D. Recently, multiple lines of investigation have demonstrated downregulation of CTL response associated with diabetogenic auto-reactive T cell by antagonist peptide vaccination is an efficacy approach for T1D prophylaxis and therapy. Administration of self-peptides or altered peptide ligands (APLs) for the induction of diabetogenic CD8+ T cell tolerance provides a new strategy for diabetes immunotherapy. The advantage of peptide-specific therapy over other forms of therapy is that it lacks potential metabolic activity and can limit the range of the response to the desired pathogenic peptide epitopeswithout increasing the possibility for hyperactivation of self-reactive T cells. Recently, modulation of CTL response by manipulating T cell epitopes has been considered as a particularly attractive approach for autoimmune disease immunotherapy.Insulin was the first β-cell protein to which an autoimmune response was documented in type 1 diabetic patients, and accumulating evidence suggests it is a key target of pathogenic T-cells in both NOD mice and human. mInsB5–14 and mInsA2–10, derived from insulin were confirmed to be the immune-dominant HLA-A*0201 restrictednullCTL epitopes in the humanized HLA transgenic NOD model (NOD.β2mexpressed chimeric HLA-A*0201 molecule.HHD) whichThere are few research about modulation of CTL response by epitope or APL for T1D immunotherapy in polyclone anim