112 results about "Major histocompatibility complex" patented technology

The present invention is a method for determining the identity of the epitopes recognized by T-cells. The method consists of expressing an encoded library of candidate epitope sequences in a recipient reporter cell capable of providing a detectable signal upon cytotoxic attack from a single cognate T-cell followed by contacting the reporter cells with T-cells of interest. The reporter cells with a single indicating cytotoxic attack from a T-cell are isolated and then analyzed by next-generation sequencing in order to identify the epitope sequences. Specifically disclosed is a method in which a library of candidate epitope-encoding nucleic acids are expressed in cells which feature a membrane-bound major histocompatibility complex (MHC) protein, said library produced by transfection of plasmids featuring both a nucleotide encoding the candidate epitope and a nucleotide encoding a FRET-based fluorescent protein cleaved by granzyme.

The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I polypeptide and/or human or humanized β2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

The present invention provides, inter alia, a method for generating a genome-wide epigenomic map, comprising a correlation between methylation variable CpG positions (MVP) and genomic DNA sample types. MVP are those CpG positions that show a variable quantitative level of methylation between sample types. Particular genomic regions of interest (ROI) provide preferred marker sequences that comprise multiple, and preferably proximate MVP, and that have novel utility for distinguishing sample types. The epigenic maps have broad utility, for example, in identifying sample types, or for distinguishing between and among sample types. In a preferred embodiment the epigenomic map is based on methylation variable regions (MVP) within the major histocompatibility complex (MHC), and has utility, for example, in identifying the cell or tissue source of a genomic DNA sample, or for distinguishing one or more particular cell or tissue types among other cell or tissue types. Analysis of epigenetic characteristics of one, or of a set of nucleic acid sequences, in the context of an inventive epigenomic map, allows for the determination of an origin of the nucleic acids.

This invention relates to methods of using human dendritic cells to present antigens for the induction of antigen-specific T cell-mediated immune responses. In particular, it relates to the isolation of dendritic cells from human blood, exposing the cells to antigens, co-culturing the antigen-pulsed dendritic cells with gammadelta-T cell receptor-positive-T cells (gammadelta-TCR<+> T cells) obtained from unprimed or weakly primed individuals for the stimulation of antigen-specific T cell proliferative and cytotoxic activities. The dendritic cell antigen presentation system described herein has a wide range of applications, including but not limited to, activation and expansion of large numbers of antigen-specific major histocompatibility complex-unrestricted T cells for use in adoptive cellular immunotherapy against infectious diseases and cancer.

The invention discloses a tumor neoantigen detection method and device based on next-generation sequencing, and a storage medium. The tumor neoantigen detection method disclosed by the invention comprises the following steps of variation detection, MHC (Major Histocompatibility Complex) molecular identification, variation annotation, variation peptide fragment prediction, variation peptide fragment MHC/II type affinity prediction, antigen expression abundance detection, clonality analysis and candidate tumor neoantigen comprehensive scoring sorting, wherein the candidate tumor neoantigen comprehensive scoring sorting comprises the step of scoring sorting on the neoantigen according to MHC affinity, antigen expression abundance and clonality according to a formula I. According to the tumorneoantigen detection method, a next-generation sequencing comparison file is used as a basis to carry out mutation and MHC detection, in addition, the candidate tumor neoantigen is scored from three dimensions including MHC I/II type affinity, antigen expression abundance and clonality so as to the screen high-quality tumor neoantigen, and a foundation is laid for immunotherapy on the basis of thetumor neoantigen.

The present invention provides humanized, chimeric and human anti-CD74 antibodies, CD74 antibody fusion proteins, immunoconjugates, vaccines and bispecific that bind to CD74, the major histocompatibility complex (MHC) class-II invariant chain, Ii, which is useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies, other malignancies in which the cells are reactive with CD74, and autoimmune diseases, and methods of treatment and diagnosis.

The invention provides an African swine fever cytotoxic T lymphocyte (CTL) epitope polypeptide and an application thereof, and belongs to the technical field of preparation of polypeptide vaccines. According to the invention, polypeptides which are derived from African swine fever virus (ASFV) and can be stably bound by major histocompatibility complex class I (MHC I) are screened through a bioinformatic method and a method for identifying binding motifs of MHC I, and the screened polypeptide has the capability of starting CD8+T cells to generate immune response and stimulating organisms to specifically generate CTL, wherein an amino acid sequence of the polypeptide is shown in any one of from SEQ ID NO.1 to SEQ ID NO.18. The polypeptide provided by the invention can be used for preparingAfrican swine fever specific epitope vaccines or polypeptide vaccines, has high safety and good specificity, and has a potential application value in prevention and control work of African swine fever.

The invention discloses an automatic protection method for a computer virus. A protection program is constructed and installed in a computer by taking a human immune system as a model; and the protection program realizes immunity of the computer from a virus program by monitoring a new program, performing engineering reversing, judging a diffusive replication statement, acquiring a replication target path, automatically creating a high-authority antibody folder, simulating byte count register (BCR) homologous judgment in the human immune system, presenting a peptide section by using a major histocompatibility complex (MHC) II and releasing an antibody by using a cell B. Compared with the prior art, the method has the advantages that: a virus database and manual scanning are not needed, network interconnection is not needed to update the virus database, the antibody is automatically produced aiming at a computer malicious program, and the computer malicious program is effectively intercepted, so the computer has active defense capacity to the virus. Tests show that the interception rate of the tested virus can reach over 99.7 percent.

The present invention relates to a gene for predicting or diagnosing the prognosis of early-stage breast cancer and to a use thereof, and more specifically relates to a genetic marker for predicting or diagnosing the prognosis of breast cancer, including TRBC1 (T cell receptor beta constant 1), BTN3A2 (butyrophilin, subfamily 3, member A2) or HLA-DPA1 (major histocompatibility complex, class II, DP alpha 1) for providing information necessary for predicting or diagnosing the prognosis of a breast cancer patient. The genetic marker of the present invention allows the prediction or diagnosis of the prognosis of a breast cancer patient, and can therefore advantageously be used for the purpose of providing a direction as to the future course of breast cancer treatment, including a decision on whether anticancer therapy is necessary.

The invention provides sgRNA or PTG (Polycistronic tRNA-gRNA), through combination with a CRISPR-Cas9 technique, a T cell antigen receptor (TCR) can be knocked out, or one or more of genes relevant tomajor histocompatibility complex (MHCI) and immunosuppression molecules can be knocked out. The invention also provides a general type CAR-T cell which can express chimeric antigen receptor (CAR) butcannot express TCR, and a preparation method of the general type CAR-T cell. The general type CAR-T cell prepared by the preparation method is suitable for heterogeneity antigen, has generality and has higher killability at the same time.

The invention discloses a high-throughput prediction method for neoantigens of pan-cancer tumor and application thereof. According to the prediction method disclosed by the invention, mutation and MHC(Major Histocompatibility Complex) detection are carried out on the basis of a next-generation sequencing original data file, and candidate tumor neoantigens are scored from multiple dimensions, so that the false positive of neoantigen screening can be reduced, and the neoantigens with high credibility can be screened out through scoring sorting. The method disclosed by the invention can be suitable for multiple cancer species, can predict the tumor neoantigen without distinguishing the cancer species, and lays a foundation for immunotherapy based on the tumor neoantigen.

The invention provides universal CD8+T cell epitope polypeptide of a chicken IBV (Infectious Bronchitis Virus) S1 protein, and belongs to the field of gene and protein engineering. The epitope polypeptides are prepared by the following steps: screening 21 epitope polypeptides in accordance with binding motif sequences in amino acid sequences of the S1 genes of the IBV virus according to the binding motif sequences of haplotype chicken major histocompatibility complex (MHC) I-type molecules; then, taking lymphocytes of three constructed SPF (Specific Pathogen Free) chicken immunized by DNA (Deoxyribonucleic Acid) recombinant plasmids of the S1 genes containing different subtype IBVs, determining the capacity of the 21 polypeptides which induce chicken splenic lymphocytes to secrete interferon-gamma by using an ELIspot (Enzyme-Linked Immunospot Assay) method, and finally, screening to obtain four universal functional T cell epitope polypeptides of IBV, wherein the sequences are respectively shown in SEQ ID NO. 1-4. The four epitope polypeptides provided by the invention are combined in use to prepare a universal vaccine for IBV. The invention further provides a method for screening the epitope of the functional T cell of the S1 protein of the IBV.

The invention relates to an MUC1-Fc polypeptide vaccine as well as a preparation method and an application thereof. The polypeptide vaccine comprises MUC1 antigen peptide containing immune globulin Fc segments, and the sequence of the peptide is represented by SEQ ID NO:1; with the adoption of the genetic engineering technology, the sequence of the MUC1 antigen peptide containing the immune globulin Fc segments is built to a carrier, and the MUC1 antigen peptide is expressed and purified in escherichia coli and coated with carriers such as lipidosome and the like so as to obtain the MUC1-Fc polypeptide vaccine. The MUC1-Fc polypeptide vaccine contains MHC (major histocompatibility complex) I and MHC II binding epitopes simultaneously, thereby being capable of breaking through MHC restrictive factors, effectively activating cytotoxic T lymphocyte (CTL) reaction, having higher killing effect on tumor cells and achieving better preventing and treating effects.

This invention discloses a method for early stage diagnosis of uterine neck cancer related to HPV16, 18 early and late stage protein antibody by using specific polypeptide. It utilizes that the expression of MHC major histocompatibility complex I, II antigen and the existence of tumour and the defection before cancerization of uterine cervix are intimately involved, especially the HLA which is associated with the cancerization of uterine cervix esoderma cell, (CIN) immersed cancer, and cervical carcinoma is human leukocyte antigen molecule, and all immunity decomposing in the body with a series of complex cell-conducting changes into little polypeptide molecule combining break and is connected with MHC. The HLA-DR antigen in the high uterine cervix defecting time CIN III markedly increases expression and regulate and control. The cellular immunity medium (CMI) is immune to HVS, E2, E4, E6 and E7 polypeptide and is connected with antibody of HPV16 early protein by screening polypeptide sequence which is associated with height and antibody.

The invention discloses a garrupa MHC (Major Histocompatibility Complex) IIB gene as well as a cloning method and application thereof. The nucleotide sequence of the garrupa MHC IIB gene is shown as SEQ ID NO:1, and the amino acid sequence of protein encoded by the gene is shown as SEQ ID NO:2. In the invention, by using a homologous cloning method, the MHC IIB gene is separated from garrupa, 12 different MHC IIB gene types are identified, the correlation between the polymorphism and the disease resistance of the MHC IIB gene are analyzed, and 6 molecular marks of the MHC IIB gene relevant to the disease resistance of the garrupa are screened; and the cloning method is suitable for screening the marks relevant to the disease resistance of the garrupa and breeding disease-resistant species.

The present invention is directed to the discovery that allogenic or syngenic adjuvant stimulation can cause local inflammation which increases the antigen presentation capability of cells in the vicinity of adjuvant stimulation. By discovering this phenomenon, the present invention provides a novel method for augmenting the immunogencity of an antigen by conjointly administering an allogenic or syngenic MHC molecule (as a universal adjuvant) to trigger a local inflammatory reaction to enhance antigen presentation at the site of delivery.

The invention discloses a method for screening a tumor specific T cell from a TIL (tumor infiltrating lymphocyte). The method includes the steps of screening a tumor specific antigen peptide of a to-be-tested tumor patient; constructing a composite of an MHC (major histocompatibility complex) and the tumor specific antigen peptide, wherein the MHC and antigen peptide composite can be combined witha TCR (T cell receptor) of a T cell of a tumor specific antigen; adding an IFN-r positive TIL of the to-be-tested tumor patient to the MHC and antigen peptide composite, performing incubation, and screening the tumor specific T cell. The invention also provides a tumor specific polypeptide screened by the method, and application of the screened tumor specific T cell and the polypeptide in products related to cancer therapy. By the method, the tumor specific T cell and the tumor specific polypeptide can be efficiently screened out, and accordingly, an effective choice for tumor immunotherapy is provided.

An object of the present invention is to stimulate a T cell without using a peptide/MHC tetramer. In the present invention, the step of supplying an antigen peptide to a T cell having a T cell receptor (TCR) that can recognize the antigen peptide on cell surface to form a complex of a major histocompatibility complex (MHC) molecule on the cell surface of the T cell and the antigen peptide is used, and the T cell is stimulated through recognition by TCR of the antigen peptide as the MHC molecule-antigen peptide complex on the cell surface of the same T cell. Such a stimulating and activating method would be applicable to not only T cells, but also various cells. According to the present invention, an antigen-specific T cell can be identified without establishing any antigen-specific T cell strain, and without using such a reagent as MHC/peptide tetramer. That is, a cancer-specific T cell can be efficiently and conveniently identified.

Compositions comprising a cell in which a molecular complex with high affinity for its cognate ligand is bound to the surface of the cell are provided. To form the molecular complexes, extracellular domains of transmembrane heterodimeric proteins, particularly T cell receptor and major histocompatibility complex proteins, can be covalently linked to the heavy and light chains of immunoglobulin molecules. The molecular complexes can be used, inter alia, to detect and regulate antigen-specific T cells and as therapeutic agents for treating disorders involving immune system regulation, such as allergies, autoimmune diseases, tumors, infections, and transplant rejection. Optionally, identical antigenic peptides can be bound to each ligand binding site of a molecular complex.