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

A technology of HLA-A and insulin, which is applied in the direction of peptides, etc., can solve the problems of difficult to grasp the scale of immune response type conversion and unpredictable final outcome of the disease, and achieve easy large-scale preparation and purification, reduce research costs, and reduce workload Effect

A technology of HLA-A and insulin, which is applied in the direction of peptides, etc., can solve the problems of difficult to grasp the scale of immune response type conversion and unpredictable final outcome of the disease, and achieve easy large-scale preparation and purification, reduce research costs, and reduce workload Effect

CN101974071BInactive Publication Date: 2012-11-21ARMY MEDICAL UNIV
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  • Insulin B chain HLA-A*0201 restrictive CTL epitope modified peptide ligand and acquisition method and application thereof
  • Insulin B chain HLA-A*0201 restrictive CTL epitope modified peptide ligand and acquisition method and application thereof
  • Insulin B chain HLA-A*0201 restrictive CTL epitope modified peptide ligand and acquisition method and application thereof

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Embodiment Construction

[0024] Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.

[0025]1. Establishment of TCR-HLA-A*0201-mInsB 5-14 A structural model of the ternary complex identifying the native epitope mInsB 5-14 Potential TCR main action site in

[0026] Using Insight II software to first establish the natural epitope mInsB 5-14 (amino acid sequence is HLCGPHLVEA) and HLA-A*0201 binary complex (pMHC) structure model, and then further establish the ternary complex structure model of pMHC and TCR ( figure 1 ), analyzing the natural epitope mInsB 5-14 Amino acid residues that may interact with TCR. The results showed that the natural epitope mInsB 5-14 The 5th position and the 6th position in both are potential TCR main action sites, but the proline residue at the 5th position has a greater impact on the conformation of the polypeptide, so the present invention only uses the 6th position as Modification site....

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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 Ξ² 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...

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Application Information

Patent Timeline
21 Nov 2012
Publication
CN101974071B
IPC
C07K7/06
Inventors
ηŽ‹θŽ‰; θˆ’ι©°