Disclosed are methods of isolating a TCR having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation, the method comprising: identifying one or more genes in the nucleic acid of a cancer cell of a patient, each gene containing a cancer-specific mutation that encodes a mutated amino acid sequence; inducing autologous APCs of the patient to present the mutated amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated amino acid sequence; selecting the autologous T cells; and isolating a nucleotide sequence that encodes the TCR from the selected autologous T cells, wherein the TCR has antigenic specificity for the mutated amino acid sequence encoded by the cancer-specific mutation. Also disclosed are related methods of preparing a population of cells, populations of cells, TCRs, pharmaceutical compositions, and methods of treating or preventing cancer.

The present invention is related to peptides that can be used to reduce the immune response against FVIII or to induce tolerance to human FVIII in patients with, e.g., hemophilia A. Furthermore, the peptides can be used for immunodiagnostic purposes to detect FVIII-specific CD4.sup.+ T cells to monitor patients with hemophilia A during replacement therapy and during immune tolerance induction therapy.

Compositions consisting of bioactive molecules derived from the microbiota of a mammal are provided herein. When administered orally with a colonic delivery system, the compositions are useful for the prophylaxis and treatment of diseases, in particular inflammatory, autoimmune and infectious diseases. The compositions comprise combinations of small molecules and bacterial antigens formulated in colonic delivery systems. Use of the compositions results in any or all of: induction of immune tolerance; strengthening of the gut mucosal barrier integrity; reduction of inflammation; and amelioration of a disease state caused by inflammation, an autoimmune reaction or an infectious agent.

Disclosed herein are methods for diagnosing or predicting B-cell rejection in a subject. In one example, for assessing transplant rejection, the method includes determining an antigen presenting index by comparing uptake of a donor antigen to uptake of a reference antigen in a biological sample obtained from the subject. In another example, for assessing GVHD, the method includes determining an antigen presenting index by comparing uptake of a recipient antigen to uptake of a reference antigen in a biological sample obtained from the subject.

The present disclosure relates to pharmaceutical compounds and compositions and methods for treating an allergy and Crohn's disease. Methods for treating an allergy can include (a) predicting potential epitopes based proteomes of microbiome and that of an allergen, (b) filtering the potential epitopes obtained in step a) to result in a list of epitopes; and (c) reengineering the list of epitopes obtained in step b) to result in the new epitope. Methods for treating Crohn's disease can include (a), identifying one or more binding regions of an HLA class II protein and/or hemagglutinin to I2 superantigen; (b) determining a first peptide sequence corresponding to the one or more binding regions, and (c) producing a peptide inhibitor having a second peptide sequence that is a mutation of the first peptide sequence, wherein the second peptide sequence has a stronger binding affinity to the I2 superantigen than the first peptide sequence.

There is provided herein, the use of mammalian derived HLA class I molecule for in vitro peptide exchange. For example, there is provided a method of producing an HLA class I molecule complexed to a pre-selected peptide comprising: (a) providing a mammalian derived HLA class I molecule complexed to an existing peptide; (b) incubating, in vitro, the HLA class I molecule complexed to the existing peptide with the pre-selected peptide, wherein the pre-selected peptide is at a concentration sufficient to replace the existing peptide to produce the HLA class I molecule complexed to the pre-selected peptide; and the HLA class I molecule comprises α1, α2, α3 and β2m domains.

Provided herein are antibodies that selectively bind to HLA-G and compositions comprising the antibodies. Also provided are methods of using the antibodies, such as therapeutic and diagnostic methods.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Effectiveness of a neoepitope-based immunotherapeutic composition against a tumor can be increased by predicting the surface presentation of the neoepitope bound to the HLA molecule of the tumor cell. Surface presentation levels of neoepitopes can be predicted by identifying any changes in omics data of the tumor cell that may affect the expression or surface trafficking of the HLA molecule and that may affect binding affinities of neoepitopes to the HLA molecule.

Adaptive immune responses rely on the ability of cytotoxic T cells to identify and eliminate cells displaying disease-specific antigens on human leukocyte antigen (HLA) class I molecules. Investigations into antigen processing and display have immense implications in human health, disease and therapy. To extend understanding of the rules governing antigen processing and presentation, immunopurified peptides from B cells, each expressing a single HLA class I allele, were profiled. A resource dataset containing thousands of peptides bound to distinct class I HLA-A, -B, and -C alleles was generated by implementing a novel allele-specific database search strategy. Applicants discovered new binding motifs, established the role of gene expression in peptide presentation and improved prediction of HLA-peptide binding by using these data to train machine-learning models. These streamlined experimental and analytic workflows enable direct identification and analysis of endogenously processed and presented antigens.