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.

De novo designed polypeptides that bind to IL-2 receptor β.sub.c heterodimer (IL-2Rβ.sub.c), IL-4 receptor α.sub.c heterodimer (IL-4Rα.sub.c), or IL-13 receptor α subunit (IL-13Rα) are disclosed, as are methods for using and designing the polypeptides.

Antibodies which block binding of hPD-1 to hPD-L1 or hPD-L2 and their variable region sequences are disclosed. A method of increasing the activity (or reducing downmodulation) of an immune cell through the PD-1 pathway is also disclosed.

Embodiments of this invention include methods for detecting in vitro the presence of Memory B cells in peripheral blood mononuclear cells (PBMCs) that produce antibodies reactive to CNS antigens associated with Multiple Sclerosis (MS). Stimulating PBMCs from patients with MS by a polyclonal stimulating agent promotes the ability of B-lymphocytes, when exposed to a CNS antigen, to produce antibodies specific for the CNS antigen. In contrast, stimulating PBMCs from subjects without MS do not produce such responses.

Methods are provided to separately isolate antigen-binding T cells and antigen-activated T cells derived from a starting population of peripheral blood mononuclear cells, and to identify overlapping T cell receptor clonotypes. Antigens include personal and shared neoantigens as well as cancer-testis antigens. The T cell receptor clonotypes can be further used to develop cancer treatment therapies.

In one aspect, disclosed herein is a method for evaluating the immunogenicity of a test substance in a short period of time by using, as an indicator of the immunogenicity of the test substance, the proportion of IL-2-secreting cells in a T cell population (preferably a CD4.sup.+ T cell population) at a time point during the early stage of IL-2 secretion after stimulation of the T cell population with the test substance (preferably 24 hours to 72 hours after the stimulation with the test substance).

The invention includes compositions comprising a therapeutic agent that decreases the population of pathological CD4g13 T cells, g13Th1 or g13Th2, in a subject and compositions comprising a therapeutic agent that increases the population of protective CD4g13 T cells, g13Th1 or g13Th2, in a subject. The invention also includes methods for treating an inflammatory or autoimmune disease in a subject by administering to the subject an effective amount of a therapeutic agent that increases the population of protective CD4g13 T cells, methods for detecting a protective or pathological immune response and methods for stimulating a protective CD4g13 T cell-mediated immune response to a cell population or a local tissue or organ in a subject in need thereof. The invention further includes a kit for diagnosing a pathological or protective g13Th1 or g13Th2 T cell responses in a subject.

Biomarker panels for the prediction of patient response to immunotherapy, and methods of use thereof.

The present disclosure describes a murine T cell 3A9 comprising a polynucleotide sequence encoding human LAG3, and a murine IL-2 promotor operably associated with a reporter gene. The disclosure also describes a cell-based potency assay for measuring LAG3 antagonist activity using a co-cultured system with the murine T cells and LK35.2 murine B cells, and hen egg lysozyme peptide.

De novo designed polypeptides that bind to IL-2 receptor β.sub.c heterodimer (IL-2Rβ.sub.c), IL-4 receptor α.sub.c heterodimer (IL-4Rα.sub.c), or IL-13 receptor α subunit (IL-13Rα) are disclosed, as are methods for using and designing the polypeptides.