PMHC binding agent and application thereof

By delivering four RNA molecules via lipid nanoparticles, the expression of antigen peptide-major histocompatibility complex type II molecules was enhanced and dynamically monitored, solving the problems of insufficient expression levels and monitoring difficulties in existing technologies, and realizing the specific activation of target cell receptors and reliable monitoring of immune responses.

CN121891518APending Publication Date: 2026-04-21BEIHANG UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
BEIHANG UNIV
Filing Date
2026-01-23
Publication Date
2026-04-21

AI Technical Summary

Technical Problem

Existing technologies are insufficient to effectively enhance the expression level of antigen peptide-major histocompatibility complex type II molecular proteins, and lack dynamic monitoring methods in vivo, making it difficult to link immune outcomes with mechanisms.

Method used

Four RNA molecules were encapsulated in lipid nanoparticles and delivered to cells or organisms, including an antigenic peptide, a DRB1*13:02 β chain binding segment to mouse I-Eb, nucleic acid molecules encoded by CD28 and CD3ζ proteins, CMV, CD74, an antigenic peptide, a nucleic acid molecule encoded by a red-visible fluorescent protein, a nucleic acid molecule encoded by a peptide sequence of the CD4 and T cell surface receptor binding regions, and a nucleic acid molecule encoded by mCD40L and a binding peptide that recognizes pMHC. The expression of pMHC molecules was enhanced and dynamically tracked using CRISPR-Cas9 gene editing technology.

Benefits of technology

This study achieved specific activation of receptors on the surface of target cells, increased pMHC molecule expression, reduced pathogenic MHC-II molecule expression, dynamically monitored the expression of binding agent-encoded proteins, and provided reliable conclusions on the immune response.

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Abstract

The invention discloses a pMHC binding agent and application thereof. The antigen peptide-major histocompatibility complex binding agent comprises four RNA molecules, wherein the first RNA molecule comprises an antigen peptide, a DRB1 * 13: 02 beta chain, a mouse I-Eb binding segment and nucleic acid molecules coded by CD28 and CD3 zeta proteins of transmembrane and intracellular segments; the second RNA molecule comprises CMV, CD74, an antigen peptide and a nucleic acid molecule coded by a red visible spectrum fluorescent protein; the third RNA molecule comprises CD4 and a nucleic acid molecule coded by a T cell surface receptor binding region peptide sequence; and the fourth RNA molecule comprises mCD40L and a nucleic acid molecule coded by a binding peptide fragment for recognizing pMHC. According to the present invention, the antigen peptide-major histocompatibility complex II type molecule and the T cell surface receptor can be efficiently and specifically combined so as to promote the activation of the target cell surface receptor so as to achieve the efficient autoimmune reaction;
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Claims

1. An antigen peptide-major histocompatibility complex (MHC) binding agent, characterized in that: It includes four RNA molecules. The first RNA molecule includes an antigenic peptide, DRB1*13:02 β chain, and murine IE. b The first RNA molecule consists of a binding segment and transmembrane and intracellular segments encoded by CD28 and CD3ζ proteins; the second RNA molecule includes nucleic acid molecules encoded by CMV, CD74, antigenic peptides, and red-visible fluorescent proteins; the third RNA molecule includes nucleic acid molecules encoded by CD4 and peptide sequences of the T cell surface receptor binding region; and the fourth RNA molecule includes nucleic acid molecules encoded by mCD40L and a binding peptide that recognizes pMHC.

2. The antigen peptide-major histocompatibility complex binder according to claim 1, characterized in that: The nucleic acid sequence of the first RNA molecule is shown in SEQ ID NO.

1.

3. The antigen peptide-major histocompatibility complex binder according to claim 1, characterized in that: The nucleic acid sequence of the second RNA molecule is shown in SEQ ID NO.

2.

4. The antigen peptide-major histocompatibility complex binder according to claim 1, characterized in that: The nucleic acid sequence of the third RNA molecule is shown in SEQ ID NO.

3.

5. The antigen peptide-major histocompatibility complex binder according to claim 1, characterized in that: The nucleic acid sequence of the fourth RNA molecule is shown in SEQ ID NO.

4.

6. The antigen peptide-major histocompatibility complex binder according to claim 1, characterized in that: RNA molecules are delivered into cells or organisms by encapsulating them with lipid nanoparticles.

7. The use of the antigen peptide-major histocompatibility complex binder according to any one of claims 1-6 in the preparation of a drug for treating chronic inflammation.

8. A drug for treating chronic inflammation, characterized in that: Includes the antigen peptide-major histocompatibility complex binder according to any one of claims 1-6.

9. The medicament according to claim 8, characterized in that: Antigen peptide-major histocompatibility complex binders are delivered to cells or organisms after being encapsulated in lipid nanoparticles.