Insulin chain A human leukocyte antigen (HLA)-A*0201 restrictive cytotoxic T lymphocyte (CTL) epitope altered peptide ligand and application thereof

Abstract

The invention discloses an insulin chain A human leukocyte antigen (HLA)-A*0201 restrictive cytotoxic T lymphocyte (CTL) epitope altered peptide ligand (APL) which is obtained by replacing sixth amino acid L-Cys in insulin chain A HLA-A*0201 restrictive natural CTL epitope mInsA2-10 of humanized non-obese diabetic (NOD) mice with D-Cys. The amino acid sequence of the APL is shown as SECIDNo.1L; the natural CTL epitope has high cross reactivity with human epitope, and the APL has an obvious characteristic of inhibiting natural epitope specificity CTL response in the extracorporal cellar immunefunction experiment of the humanized NOD mice and the peptide has the characteristics that the peptide is easy to prepare and purify in a large scale and can be used safely, so that the APL can be independently applied to the development of I-type diabetes mellitus therapeutic antagonist peptide vaccine or is combined with other immunodominance autoantigen epitopes or APL to be applied to the development of I-type diabetes mellitus therapeutic antagonist peptide vaccine, and has potential and good development and application prospect in the field of human I-type diabetes mellitus treatment.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to an antigen epitope modified peptide ligand (altered peptide ligand, APL), in particular to the HLA-A*0201 restricted CTL epitope APL of insulin A chain (mInsA). Background technique [0002] Type I diabetes (Type 1 diabetes, T1D) is a type of autoimmune disease mediated by T lymphocytes and characterized by the elimination of insulin-producing β-cells, which mostly occurs in children and adolescents. At the same time, since hyperglycemia may further cause eye, blood, cardiovascular and nervous system diseases, it is also very important to prevent and control pathological autoimmune symptoms such as pancreatic tissue destruction. At present, T1D is mainly treated with exogenous insulin replacement, which is expensive and has many side effects. Therefore, it is urgent to find an interventional treatment strategy that can effectively down-regulate the autoimmune state. [0003] In recent ye...

AI Technical Summary

Problems solved by technology

CD4 freshly isolated from islets of NOD mice with T1D alone + Adoptive transfer of T cells to NOD scid mice did not induce T1D; however, the islets infiltrated CD8 + T cells, but can knock out CD4 + T1D is rapidly induced in NOD or NOD scid mice of T cells, whereas knockout of CD8 + T cells or CD8α-knockout NOD mice also exhibit T1D resistance

Images