Search

CN-121974999-A - MHC I autoantigen peptide for inducing immune tolerance and application thereof

CN121974999ACN 121974999 ACN121974999 ACN 121974999ACN-121974999-A

Abstract

The invention provides an MHC class I autoantigen peptide for inducing immune tolerance, the amino acid sequence of which is shown as SEQ ID NO. 4. The invention also provides a DNA molecule for encoding the MHC class I autoantigen peptide for inducing immune tolerance. The invention also provides a recombinant vector which contains the DNA molecule. The invention also provides application of the polypeptide in preparing a medicament for preventing or treating autoimmune diseases. The self-antigen peptide provided by the invention is derived from the self-antigen peptide presented on the surface of the activated CD4 + T cell, and can be specifically identified by the self-reactive CD8 + T cell, so that immune response is induced and the regulation and control on pathogenic T cells are realized. Through the mechanism, the antigen peptide can be used for inducing immune tolerance of organisms and has application value in improving or treating autoimmune diseases.

Inventors

  • LU LINRONG
  • Bai Yadan

Assignees

  • 上海交通大学医学院附属仁济医院

Dates

Publication Date
20260505
Application Date
20260407

Claims (10)

  1. 1. An MHC class I autoantigen peptide for inducing immune tolerance, which has an amino acid sequence shown in SEQ ID NO. 4.
  2. 2. A DNA molecule encoding the MHC class I autoantigen peptide of claim 1 for inducing immune tolerance.
  3. 3. A recombinant vector comprising the DNA molecule of claim 2.
  4. 4. A host cell comprising the recombinant vector of claim 3.
  5. 5. An expression system comprising the recombinant vector of claim 3 or the DNA molecule of claim 2 integrated into the genome.
  6. 6. Use of an MHC class I autoantigen peptide for inducing immune tolerance as claimed in claim 1 in the manufacture of a medicament for the prophylaxis or treatment of an autoimmune disease.
  7. 7. The use according to claim 6, wherein the medicament is a vaccine.
  8. 8. A pharmaceutical composition, characterized in that the effective components of the pharmaceutical composition are the MHC class I autoantigen peptide for inducing immune tolerance as shown in the claim 1, the MHC class I autoantigen peptide for inducing immune tolerance as shown in the SEQ ID NO. 2, and the MHC class I autoantigen peptide for inducing immune tolerance as shown in the SEQ ID NO. 3.
  9. 9. The pharmaceutical composition of claim 8, wherein the composition further comprises a pharmaceutical excipient.
  10. 10. The pharmaceutical composition of claim 8, wherein the composition is in the form of a tablet, capsule or injection.

Description

MHC I autoantigen peptide for inducing immune tolerance and application thereof Technical Field The invention belongs to the biomedical field, and relates to an MHC I autoantigen peptide for inducing immune tolerance and application thereof. Background Autoimmune diseases are a group of diseases caused by abnormal recognition of self antigens by the immune system of the organism and attack on self tissues or cells, and common types include systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, type I diabetes and the like. Multiple sclerosis (Multiple Sclerosis, MS) is an autoimmune disease characterized primarily by demyelination of the central nervous system. The pathogenesis of the myelin sheath antigen is not completely elucidated, but a large number of researches show that the abnormal recognition and activation of the myelin sheath antigen by the CD4 + T cells are the core links of the occurrence and development of diseases. Activated CD4 + T cells can trigger inflammatory responses, mediate the immune system's attack on myelin, thereby destroying myelin structures of nerve axons, affecting nerve signaling function. Currently, clinical treatment of MS relies mainly on broad-spectrum immunosuppressants or monoclonal antibodies. Although the above methods can alleviate disease symptoms to some extent, due to lack of specific regulation of pathogenic CD4 + T cells, systemic immunosuppression and more serious adverse reactions are often accompanied. Therefore, the development of an accurate immunotherapy strategy capable of specifically recognizing and regulating pathogenic CD4 + T cells has important clinical value. Polypeptide drugs have low toxic and side effects, strong specificity and good biological safety, and become an important research direction for treating autoimmune diseases. However, due to the high polymorphism of TCR of CD8 + T cells and the antigen peptide recognized by the TCR, the fact that there is a large difference between the current bioinformatics prediction result and the peptide fragment actually presented in the cell, the inability to accurately identify active polypeptides derived from activated CD4 + T cells, capable of being efficiently presented by MHC class I molecules and having an immunomodulatory function remains a key technical problem to be solved in the art. Therefore, based on the immune regulation mechanism, a group of self-antigen peptides capable of inducing specific immune tolerance are obtained through screening by experimental means, and the method has important significance in developing a new generation of accurate immune regulation strategy and improving clinical prognosis of autoimmune diseases such as multiple sclerosis and the like. Disclosure of Invention Aiming at the technical problems in the prior art, the invention provides an MHC I self-antigen peptide for inducing immune tolerance and application thereof, and the MHC I self-antigen peptide for inducing immune tolerance and application thereof aim to solve the technical problem that medicines in the prior art have poor effect of treating autoimmune diseases. The invention provides an MHC class I autoantigen peptide for inducing immune tolerance, the amino acid sequence of which is shown as SEQ ID NO. 4. Specifically, the amino acid sequence shown in SEQ ID NO. 4 is RNFIFSRL. In some embodiments, the autoantigen peptides of the invention can be obtained by conservative amino acid substitutions. Such conservative amino acid substitutions include, but are not limited to, one or more of the following substitutions, N by Q, S by T, R by K, and I and L. The antigen peptide obtained by the substitution can still be recognized by CD8 + T cells and induce immune response, thereby realizing the regulation and control of pathogenic T cells. Thus, the antigenic peptides obtained via the conservative amino acid substitutions are equally useful in the prevention or treatment of autoimmune diseases. The invention also provides a DNA molecule encoding the above MHC class I autoantigen peptide for inducing immune tolerance. The invention also provides a recombinant vector which contains the DNA molecule. The invention also provides a host cell comprising the recombinant vector. The invention also provides an expression system which contains the recombinant vector or the DNA molecule integrated with an exogenous source in a genome. The invention also provides application of the polypeptide in preparing a medicament for preventing or treating autoimmune diseases. The invention also provides a pharmaceutical composition, the effective components of which are the MHC class I autoantigen peptide shown in SEQ ID NO. 4 and used for inducing immune tolerance, the MHC class I autoantigen peptide shown in SEQ ID NO. 2 and used for inducing immune tolerance, and the MHC class I autoantigen peptide shown in SEQ ID NO. 3. Furthermore, the composition also contains pharmaceutical excipients. Further, the composit