CN111574615A - TCR enrichment clone type and acquisition method and application thereof - Google Patents
TCR enrichment clone type and acquisition method and application thereof Download PDFInfo
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- CN111574615A CN111574615A CN202010445718.7A CN202010445718A CN111574615A CN 111574615 A CN111574615 A CN 111574615A CN 202010445718 A CN202010445718 A CN 202010445718A CN 111574615 A CN111574615 A CN 111574615A
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- 238000000034 method Methods 0.000 title claims abstract description 13
- 229960005486 vaccine Drugs 0.000 claims abstract description 22
- 238000011161 development Methods 0.000 claims abstract description 15
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 5
- 241001678559 COVID-19 virus Species 0.000 claims description 9
- 210000004027 cell Anatomy 0.000 claims description 9
- 241000700605 Viruses Species 0.000 claims description 8
- 238000012163 sequencing technique Methods 0.000 claims description 5
- 239000012636 effector Substances 0.000 claims description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims description 3
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 claims description 2
- 239000000427 antigen Substances 0.000 abstract description 11
- 102000036639 antigens Human genes 0.000 abstract description 10
- 108091007433 antigens Proteins 0.000 abstract description 10
- 238000011160 research Methods 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 208000025721 COVID-19 Diseases 0.000 description 4
- 241000711573 Coronaviridae Species 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 230000008092 positive effect Effects 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
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- 206010012735 Diarrhoea Diseases 0.000 description 1
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- 208000000112 Myalgia Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 108010083312 T-Cell Antigen Receptor-CD3 Complex Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
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- 230000007547 defect Effects 0.000 description 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
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- 208000014674 injury Diseases 0.000 description 1
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- 230000000474 nursing effect Effects 0.000 description 1
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- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2509/00—Methods for the dissociation of cells, e.g. specific use of enzymes
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Abstract
The invention relates to the technical field of biological medicines, and particularly discloses a TCR enrichment clonotype and an acquisition method and application thereof, wherein the amino acid sequence of the TCR enrichment clonotype is CAVNSYNTDKLIF _ CATSREEDNTYEQYF, which can provide antigen epitope for vaccine development and specific recognition, so that the TCR enrichment clonotype can be used for guiding vaccine development and providing direction and theoretical basis for vaccine development and research.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to a TCR enrichment clonotype and an acquisition method and application thereof.
Background
The outbreak of new coronavirus (2019-novel coronavirus, 2019-nCoV) infection poses a serious threat to global public health. The disease caused by 2019-nCoV is formally named COVID-19(coronavirus disease 2019) by World Health Organization (WHO). COVID-19 clinically manifests as pneumonia, fever, cough, muscle pain, fatigue, diarrhea, and death in severe cases. The WHO report shows that 2019-nCoV has caused a world pandemic. Vaccination is an effective means for preventing viral infection epidemics, but there is no new coronavirus vaccine (hereinafter referred to as new coronavirus vaccine) at present. At present, the treatment means mainly supports nursing aiming at the COVID-19 virus which is rapidly spread by public, and antiviral drugs, antibodies, vaccines and the like aiming at the COVID-19 are still in the clinical experiment stage and are not successfully developed. The same method as SARS in the current year is mostly adopted for symptomatic treatment, and the inflammatory reaction caused by the immune system is suppressed by hormone, but the human body is also very fragile and difficult to be protected from injury. There is an urgent need for effective vaccine development to contain the outbreaks of viruses worldwide.
T cell (antigen) receptors (TCRs), which are characteristic markers of all T cell surfaces, bind to CD3 by non-covalent bonds, forming a TCR-CD 3 complex. The role of the TCR is to recognize an antigen. The TCR is a heterodimer formed by two different peptide chains and consists of alpha and beta peptide chains, and each peptide chain can be divided into a variable region (V region), a constant region (C region), a transmembrane region, a cytoplasmic region and the like; characterized by a short cytoplasmic domain. The TCR molecule belongs to the immunoglobulin superfamily, and the antigen specificity exists in the V region; the V regions (V α, V β) in turn have three hypervariable regions CDR1, CDR2, CDR3, of which the largest variation in CDR3 directly determines the antigen binding specificity of the TCR. When the TCR recognizes the MHC-antigen peptide complex, the CDRs 1, 2 recognize and bind to the side walls of the antigen binding groove of the MHC molecule, while the CDR3 binds directly to the antigen peptide. The TCR enrichment clonotypes provided by the invention have positive effects on specific recognition of antigen epitopes through the common CDR3 variable region, and can be used for guiding vaccine development and providing direction and theoretical basis for vaccine development and research.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a TCR enrichment clonotype and an acquisition method and application thereof.
In order to achieve the above object, the present invention discloses a TCR-enriched clonotype having an amino acid sequence of CAVNSYNTDKLIF _ CATSREEDNTYEQYF.
The invention also discloses a method for acquiring the TCR enrichment clonotype, which comprises the following steps:
s1, collecting a peripheral blood mononuclear cell sample of the cured virus infected patient;
s2, carrying out TCR/BCR V (D) J immune repertoire sequencing analysis on the collected sample, and finding out a common CDR3 variable region;
s3, detecting the cell clonotype distribution with high enrichment degree of the cured virus infected patient, thereby obtaining the TCR enrichment clonotype.
Wherein the TCR-enriched clonotypes are enriched in cell clusters of effector CD8+ T cells.
The invention also discloses application of the TCR enrichment clonotype in guiding vaccine development.
Wherein the vaccine is 2019-nCoV vaccine.
The beneficial technical effects are as follows: the amino acid sequence of the TCR enrichment clonotype is CAVNSYNTDKLIF-CATSREEDNTYEQYF, and the TCR enrichment clonotype has positive significance on the antigen epitope specifically identified through a common CDR3 variable region, so that the TCR enrichment clonotype can be used for guiding vaccine development and provides a direction and theoretical basis for vaccine development and research.
Drawings
FIG. 1 is a flow chart of a method for obtaining TCR-enriched clonotypes of the invention,
FIG. 2 is a schematic representation of the location of TCR-enriched clonotypes of the invention and their degree of enrichment in TCR cells.
Detailed Description
In order to make the technical solutions of the present invention better understood, the present invention is further described in detail below with reference to the accompanying drawings.
The invention provides a TCR enrichment clonotype, and the amino acid sequence of the TCR enrichment clonotype is CAVNSYNTDKLIF-CATSREEDNTYEQYF.
As shown in fig. 1 and fig. 2, in this embodiment, the method for obtaining a TCR-enriched clonotype specifically includes the following steps:
s1, collecting a peripheral blood mononuclear cell sample of the cured virus infected patient;
s2, carrying out TCR/BCR V (D) J immune repertoire sequencing analysis on the collected sample, and finding out a common CDR3 variable region;
s3, detecting the distribution of cell clonotypes with high enrichment degree of the cured virus infected patient, thereby obtaining the TCR enrichment clonotypes.
In the embodiment, single nuclear cells of peripheral blood of four 2019-nCoV virus infected patients are selected as sampling samples, then TCR/BCR V (D) J immune repertoire sequencing analysis is carried out on the sampling samples, although the sequencing analysis result has no common cell clonotypes, a common CDR3 variable region exists, and the TCR enrichment clonotypes enriched in effector CD8+ T cell clusters are obtained by detecting the cell clonotype distribution with high enrichment degree of the virus infected patients, so that the TCR enrichment clonotypes have positive effect on specific recognition antigen epitopes through the common CDR3 variable region.
In this embodiment, the TCR-enriched clonotypes described above are applied to guide vaccine development, particularly to guide 2019-nCoV vaccine development, and since the TCR-enriched clonotypes have a positive effect on specific recognition of antigenic epitopes through the common CDR3 variable region, the TCR-enriched clonotypes can be used for guiding vaccine development and provide a direction and theoretical basis for vaccine development and research.
The TCR-enriched clonotypes provided by the invention, the method for obtaining the same and the application thereof are described in detail above. The principles and embodiments of the present invention are explained herein using specific examples, which are presented only to assist in understanding the core concepts of the present invention. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.
Claims (5)
1. A TCR-enriched clonotype having the amino acid sequence CAVNSYNTDKLIF _ CATSREEDNTYEQYF.
2. A method of obtaining a TCR-enriched clonotype as claimed in claim 1, comprising the steps of:
s1, collecting a peripheral blood mononuclear cell sample of the cured virus infected patient;
s2, carrying out TCR/BCR V (D) J immune repertoire sequencing analysis on the collected sample, and finding out a common CDR3 variable region;
s3, detecting the distribution of cell clonotypes with high enrichment degree of the cured virus infected patient, and further obtaining the TCR enrichment clonotypes.
3. A method of obtaining a TCR-enriched clonotype as claimed in claim 2 wherein the TCR-enriched clonotype is enriched in a cell cluster of effector CD8+ T cells.
4. Use of a TCR-enriched clonotype according to claim 1 or a TCR-enriched clonotype obtained by the method of obtaining a TCR-enriched clonotype according to claim 2 or 3 for directing vaccine development.
5. Use of a TCR-enriched clonotype as claimed in claim 4 for directing vaccine development, wherein the vaccine is a 2019-nCoV vaccine.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010445718.7A CN111574615A (en) | 2020-05-23 | 2020-05-23 | TCR enrichment clone type and acquisition method and application thereof |
| PCT/CN2020/105806 WO2021237932A1 (en) | 2020-05-23 | 2020-07-30 | Tcr enriched clonotypes and acquisition method and application therefor |
| CN202110564597.2A CN113214383A (en) | 2020-05-23 | 2021-05-24 | TCR enrichment clone type and acquisition method and application thereof |
| US17/475,686 US12252526B2 (en) | 2020-05-23 | 2021-09-15 | TCR-enriched clonotype, acquisition method and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010445718.7A CN111574615A (en) | 2020-05-23 | 2020-05-23 | TCR enrichment clone type and acquisition method and application thereof |
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| CN111574615A true CN111574615A (en) | 2020-08-25 |
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| CN202010445718.7A Pending CN111574615A (en) | 2020-05-23 | 2020-05-23 | TCR enrichment clone type and acquisition method and application thereof |
| CN202110564597.2A Pending CN113214383A (en) | 2020-05-23 | 2021-05-24 | TCR enrichment clone type and acquisition method and application thereof |
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| CN202110564597.2A Pending CN113214383A (en) | 2020-05-23 | 2021-05-24 | TCR enrichment clone type and acquisition method and application thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023138658A1 (en) * | 2022-01-24 | 2023-07-27 | 卡瑞济(北京)生命科技有限公司 | 2019-ncov-specific t cell receptor and use thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1609196A (en) * | 2003-10-17 | 2005-04-27 | 上海普泛生物科技有限公司 | High-yield T lymphocyte cloning technology for finding tumor specific antigen and tumor specific antigen determinant |
| CN101200767B (en) * | 2007-12-05 | 2012-08-22 | 浙江大学 | Method for detecting peripheral blood specific T lymphocyte |
| CN102212888A (en) * | 2011-03-17 | 2011-10-12 | 靳海峰 | High throughput sequencing-based method for constructing immune group library |
| US11001830B2 (en) * | 2015-03-16 | 2021-05-11 | Max-Delbrück-Centrum Für Molekulare Medizin In Der Helmholtz-Gemeinschaft | Method of detecting new immunogenic T cell epitopes and isolating new antigen-specific T cell receptors by means of an MHC cell library |
| CN106632659A (en) * | 2016-08-05 | 2017-05-10 | 武汉赛云博生物科技有限公司 | EB (Epstein-Barr) virus specific TCR (T cell receptor) and recombinant lentiviral vector and application thereof |
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2020
- 2020-05-23 CN CN202010445718.7A patent/CN111574615A/en active Pending
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2023138658A1 (en) * | 2022-01-24 | 2023-07-27 | 卡瑞济(北京)生命科技有限公司 | 2019-ncov-specific t cell receptor and use thereof |
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| CN113214383A (en) | 2021-08-06 |
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Application publication date: 20200825 |