Insulin B chain HLA-A*0201 restrictive CTL epitope modified peptide ligand and acquisition method and application thereof

Abstract

The invention discloses an insulin B chain HLA-A*0201 restrictive CTL epitope altered peptide ligand (APL) and an acquisition method and application thereof. The amino acid sequence of the APL is HLCGPFLVEA, and is obtained by replacing the sixth position histidine of the natural epitope mInsB5-14 by phenylalanine. The acquisition method comprises the following steps of: establishing a TCR-HLA-A*0201-mInsB5-14 compound model, determining potential TCR acting loci in the mInsB5-14, performing monoamino acid mutation on the potential TCR acting loci, and screening candidate APL having higher affinity with the HLA-A*0201 molecules than the natural epitope and space conformation close to the natural epitope; and further identifying the APL capable of obviously reducing mInsB5-14 specificity CTL response level through cell function experiments. The APL of the invention can be used for preparing a type 1 diabetes treatment negative peptide vaccine.

Description

technical field [0001] The present invention relates to an altered peptide ligand (altered peptide ligand, APL), in particular to the insulin B chain HLA-A*0201 restricted CTL (cytotoxic T lymphocyte) epitope mInsB 5-14 The APL also involves the acquisition method and application of the APL. Background technique [0002] Type I diabetes (Type I diabetes) is an autoimmune disease mediated by lymphocytes characterized by specific damage to pancreatic β cells leading to absolute deficiency of insulin production. Type I diabetes mostly occurs in children and adolescents. Its onset is sudden. If it is not treated in time, it can lead to serious complications involving important tissues and organs such as the heart, liver, kidney, nerves, and eyes. It is the main cause of disability and premature death in children and adolescents. one. In recent years, the number of children and adolescents in my country suffering from type I diabetes has been increasing year by year, and type I...

AI Technical Summary

Problems solved by technology

Hsp60 derived from heat shock protein 60 437-460 is also a dominant autoreactive CD4 + Cell epitopes, Raz et al. obtained a more stable APL after replacing the 6th and 11th amino acids with valine at the same time. This APL can effectively induce Th1→Th2 response conversion, to a certain extent Reduce or block the immune damage of β cells, but clinical studies have shown that its effect on the prevention and treatment of type 1 diabetes varies from person to person, which may be due to the difficulty in grasping the scale of immune response type conversion. Once Th2-assisted humoral immunity is excessively strengthened Finally, the final outcome of the disease becomes unpredictable, which makes it difficult to regulate CD4 + Immune Intervention Strategies for T Cell Responses Are in Embarrassment

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