Abstract: The present disclosure provides T cell modulatory polypeptides (T-Cell-MPs) comprising a chemical conjugation site at which a KRAS epitope has been conjugated and at least one immunomodulatory polypeptide sequence that may be selected to exhibit reduced binding affinity to its cognate co-immunomodulatory polypeptide. The T-Cell-epitope conjugates are useful for modulating (e.g., increasing proliferation or cytotoxic activity) the activity of T cells specific to the conjugate epitope, and accordingly for use as therapeutics. The T-Cell-epitope conjugates find use in treating a variety of cancers associated with KRAS.

Abstract: The present disclosure provides T-cell modulatory polypeptides (TMPs) that comprise an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a ?2 microglobulin polypeptide), and a peptide that presents an epitope to a T-cell receptor. A TMP of the present disclosure is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

Abstract: The present disclosure provides T-cell modulatory polypeptides (TMPs) that comprise a MOD, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a ?2 microglobulin polypeptide), and a KRAS peptide (e.g., a KRAS peptide comprising a cancer-associated mutation) that presents an epitope to a T-cell receptor. A TMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

Abstract: The present disclosure provides antigen-presenting polypeptides, including single-chain antigen-presenting polypeptides and multimeric antigen-presenting polypeptides. The present disclosure provides nucleic acids comprising nucleotide sequences encoding antigen-presenting polypeptides of the present disclosure, as well as cells genetically modified with the nucleic acids. An antigen-presenting polypeptide of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides methods of modulating activity of a T cell.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

Abstract: The present disclosure provides Transforming Growth Factor Beta (TGF-?) polypeptide constructs and complexes that find use in, for example, therapeutic treatment of diseases including autoimmune diseases and metabolic diseases and disorders. Also described are nucleic acids that encode the constructs and complexes and methods of preparing the constructs and complexes in cell-based expression systems.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.

Abstract: The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) for the presentation of KRAS antigens in the context of a class I MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids. MAPPs of the present disclosure are useful for selectively modulating activity of T cells having T cell receptors that recognize the antigens. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including cancers.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, and one or more immunomodulatory polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising an autoimmune dis-ease-associated-associated peptide epitope, MHC class II polypeptides, and one or more immunomodulatory polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have an autoimmune disease.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, and one or more immunomodulatory polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.

Abstract: The present disclosure provides T cell modulatory polypeptides (T-Cell-MPs) comprising a chemical conjugation site and at least one immunomodulatory polypeptide sequence that may be selected to exhibit reduced binding affinity to its cognate co-immunomodulatory polypeptide. The unconjugated T-Cell-MPs may be conjugated to a molecule displaying an epitope to form a T-Cell-MP-epitope conjugate. The T-Cell-epitope conjugates are useful for modulating the activity (e.g., increasing proliferation or cytotoxic activity) of T cells specific to the conjugate epitope, and accordingly for use as therapeutics.

Abstract: The present disclosure provides Multimeric Antigen-Presenting Polypeptides (MAPPs) for the presentation of epitopes in the context of a class II MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding the MAPPs. MAPPs are useful for selectively modulating activity of T cells having T cell receptors that recognize the antigens. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including cancers, autoimmune diseases and/or allergies.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.

Abstract: The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) for the presentation of antigens in the context of a class I MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids. MAPPs of the present disclosure are useful for selectively modulating activity of T cells having T cell receptors that recognize the antigens. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including cancers, autoimmune diseases and/or allergies.

Abstract: The present disclosure provides T-cell modulatory multi-merit polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMPs) conjugated to a coronavirus epitope and comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). By presenting the coronavirus epitope and MOD to a T-cell, the T-Cell-MMP-coronavirus epitope conjugates are useful for modulating the activity (e.g., increasing proliferation or cytotoxic activity) of T-cells specific to the coronavirus peptide in an epitope selective/specific manner, and accordingly, for treating individuals with a coronavirus infection.

Abstract: The present disclosure provides antigen-presenting polypeptides, including single-chain antigen-presenting polypeptides and multimeric antigen-presenting polypeptides comprising one or more chemical conjugation sites for incorporation of, for example, epitope containing polypeptides. The present disclosure provides nucleic acids comprising nucleotide sequences encoding antigen-presenting polypeptides comprising one or more chemical conjugation sites, as well as cells genetically modified with the nucleic acids. The single-chain and multimeric antigen-presenting polypeptides and their epitope conjugates are useful for modulating the activity of a T-cell, and accordingly, the present disclosure provides methods of modulating activity of a T-cell in vitro and in vivo as a method of treatment.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.