Abstract: A methodology of producing and utilizing antibodies that recognize peptides associated with a tumorigenic or disease state, wherein the peptides are displayed in the context of HLA molecules, is disclosed. These antibodies may be utilized in therapeutic methods of mediating cell lysis.

Abstract: Featured is T cell receptor complexes designed to redirect the immune system against various diseases. The T cell receptor complexes of the invention have been engineered to recognize target antigen in a functionally bispecific nature. Fusion protein complexes and protein conjugate complexes are comprised of high affinity antigen-specific TCR and biologically active proteins and/or effector molecules. Also featured is methods of production of T cell receptor fusion and conjugate complexes as well as therapeutic compositions for use of the complexes.

Abstract: The present invention relates to polyspecific binding molecules and particularly single-chain polyspecific binding molecules that include at least one single-chain T-cell receptor (sc-TCR) covalently linked through a peptide linker sequence to at least one single-chain antibody (sc-Ab). Further disclosed are methods and compositions for testing and using the molecules.

Abstract: Antibodies are produced that recognize peptides displayed in the context of MHC molecules and thus mimic the specificity of a T cell receptor (TCR). The antibodies are produced by immunizing a host with at least one peptide/MHC complex to elicit an immune response thereto. The desired antibodies can differentiate the peptide/MHC complex from the MHC molecule alone, the peptide alone, and a complex of MHC and irrelevant peptide. Finally, the desired antibodies are isolated.

Abstract: The present invention relates to polyspecific binding molecules and particularly single-chain polyspecific binding molecules that include at least one single-chain T-cell receptor (sc-TCR) covalently linked through a peptide linker sequence to at least one single-chain antibody (sc-Ab). Further disclosed are methods and compositions for testing and using the molecules.

Abstract: The present invention relates to a methodology of producing antibodies that recognize peptides associated with a tumorigenic or disease state, wherein the peptides are displayed in the context of HLA molecules. These antibodies will mimic the specificity of a T cell receptor (TCR) but will have higher binding affinity such that the molecules may be used as therapeutic, diagnostic and research reagents. The method of producing a T-cell receptor mimic of the present invention includes identifying a peptide of interest, wherein the peptide of interest is capable of being presented by an MHC molecule. Then, an immunogen comprising at least one peptide/MHC complex is formed, wherein the peptide of the peptide/MHC complex is the peptide of interest.

Abstract: The presently disclosed and claimed invention relates to a methodology of producing and utilizing antibodies that recognize peptides associated with a tumorigenic or disease state, wherein the peptides are displayed in the context of HLA molecules. These antibodies may be utilized in therapeutic methods of mediating cell lysis.

Abstract: The present invention is related to methods of assaying potency of a vaccine composition, wherein the potency is a pre-defined minimum level of potential biological activity for the vaccine composition. The method includes providing a vaccine composition and delivering same to an antigen presenting cell, wherein the vaccine composition is processed into peptides and the peptides are presented by MHC complexes on the cell surface. An agent, such as a T cell receptor mimic, that is reactive against a specific peptide/MHC complex is provided and reacted with the vaccine-treated antigen presenting cell, whereby the agent binds to the cell surface of the vaccine-treated antigen presenting cell if the specific peptide/MHC complex recognized by the agent is present on the cell surface. A density of the specific peptide/MHC complex on the surface of the vaccine-treated antigen presenting cell is measured by agent binding.

Abstract: The present invention relates to a methodology of producing antibodies that recognize peptides associated with a tumorigenic or disease state, wherein the peptides are displayed in the context of HLA molecules. These antibodies will mimic the specificity of a T cell receptor (TCR) but will have higher binding affinity such that the molecules may be used as therapeutic, diagnostic and research reagents. The method of producing a T-cell receptor mimic of the present invention includes identifying a peptide of interest, wherein the peptide of interest is capable of being presented by an MHC molecule. Then, an immunogen comprising at least one peptide/MHC complex is formed, wherein the peptide of the peptide/MHC complex is the peptide of interest.

Abstract: The present invention is related to methods of assaying potency of a vaccine composition, wherein the potency is a pre-defined minimum level of potential biological activity for the vaccine composition. The method includes providing a vaccine composition and delivering same to an antigen presenting cell, wherein the vaccine composition is processed into peptides and the peptides are presented by MHC complexes on the cell surface. An agent, such as a T cell receptor mimic, that is reactive against a specific peptide/MHC complex is provided and reacted with the vaccine-treated antigen presenting cell, whereby the agent binds to the cell surface of the vaccine-treated antigen presenting cell if the specific peptide/MHC complex recognized by the agent is present on the cell surface. A density of the specific peptide/MHC complex on the surface of the vaccine-treated antigen presenting cell is measured by agent binding.

Abstract: The present invention relates to a methodology of producing antibodies that recognize peptides associated with a tumorigenic or disease state, wherein the peptides are displayed in the context of HLA molecules. These antibodies will mimic the specificity of a T cell receptor (TCR) but will have higher binding affinity such that the molecules may be used as therapeutic, diagnostic and research reagents. The method of producing a T-cell receptor mimic of the present invention includes identifying a peptide of interest, wherein the peptide of interest is capable of being presented by an MHC molecule. Then, an immunogen comprising at least one peptide/MHC complex is formed, wherein the peptide of the peptide/MHC complex is the peptide of interest.

Abstract: The invention provides T-cell receptor (TCR) molecules comprising a V? chain and a V? chain that bind peptides derived from the p53 protein, preferably, the human p53 protein. The TCR molecules include both heterodimeric molecules and single chain molecules which specifically bind a sequence preferably spanning about amino acid positions 264-272 of the p53 protein displayed in the context of an HLA molecule, preferably, HLA-A2.1. Also disclosed are methods for making and using such TCR molecules. The invention has a wide spectrum of useful application including therapeutic uses and use in the detection of cells expressing p53 protein.

Abstract: The invention provides T-cell receptor (TCR) molecules comprising a V? chain and a V? chain that bind peptides derived from the p53 protein, preferably, the human p53 protein. The TCR molecules include both heterodimeric molecules and single chain molecules which specifically bind a sequence preferably spanning about amino acid positions 264-272 of the p53 protein displayed in the context of an HLA molecule, preferably, HLA-A2.1. Also disclosed are methods for making and using such TCR molecules. The invention has a wide spectrum of useful application including therapeutic uses and use in the detection of cells expressing p53 protein.

Abstract: The present invention relates to novel fusion proteins comprising a bacteriophage coat protein and a single-chain T cell receptor and uses of such complexes. In one aspect, the invention relates to soluble fusion protein comprising a bacteriophage coat protein covalently linked to a single-chain T cell receptor which comprises a V-alpha chain covalently linked to a V-beta chain by a peptide linker sequence. The soluble fusion proteins of the invention are useful for a variety of applications including: 1) making a bacteriophage library for displaying single-chain T cell receptors for use in screens for identification and isolation of ligands that bind single-chain T cell receptors, and 2) methods for isolating soluble and fully functional single-chain T cell receptors from the fusion proteins.

Abstract: The present invention relates to a methodology of producing antibodies that recognize peptides associated with a tumorigenic or disease state, wherein the peptides are displayed in the context of HLA molecules. These antibodies will mimic the specificity of a T cell receptor (TCR) but will have higher binding affinity such that the molecules may be used as therapeutic, diagnostic and research reagents. The method of producing a T-cell receptor mimic of the present invention includes identifying a peptide of interest, wherein the peptide of interest is capable of being presented by an MHC molecule. Then, an immunogen comprising at least one peptide/MHC complex is formed, wherein the peptide of the peptide/MHC complex is the peptide of interest.

Abstract: The present invention relates to novel complexes of major histocompability complex (MHC) molecules and uses of such complexes. In particular, the invention relates to MHC fusion complexes that contain a MHC molecule with a peptide-binding groove and a presenting peptide covalently linked to the MHC protein. Fusion complexes of the invention are useful for a variety of applications including in vitro screens for identification and isolation of peptides that modulate activity of selected T cells, including peptides that are T cell receptor antagonists and partial agonists, methods of suppressing an immune response of a mammal and methods for inducing an immune response in a mammal.

Abstract: The present invention relates to a methodology of producing antibodies that recognize peptides associated with a tumorigenic or disease state, wherein the peptides are displayed in the context of HLA molecules. These antibodies will mimic the specificity of a T cell receptor (TCR) but will have higher binding affinity such that the molecules may be used as therapeutic, diagnostic and research reagents. The method of producing a T-cell receptor mimic of the present invention includes identifying a peptide of interest, wherein the peptide of interest is capable of being presented by an MHC molecule. Then, an immunogen comprising at least one peptide/MHC complex is formed, wherein the peptide of the peptide/MHC complex is the peptide of interest.

Abstract: Disclosed is a method of inhibiting production of IFN-? in patients having a transplanted organ. The method involves administering to the patient an amount of an angiotensin receptor-blocking compound, the amount being effective to inhibit production of IFN-? by T cells. The method can be used to treat inflammation involving an allograft, to treat chronic allograft nephropathy, and to treat other pathologies associated with allograft rejection.

Abstract: Disclosed are methods for identifying compounds that modulate an immune complex that includes a T cell receptor (TCR) and a major histocompatibility complex (MHC) antigen. The invention has many useful applications including providing high throughput screening assays for detecting compositions that can modulate an immune response.

Abstract: The present invention relates to polyspecific binding molecules and particularly single-chain polyspecific binding molecules that include at least one single-chain T-cell receptor (sc-TCR) covalently linked through a peptide linker sequence to at least one single-chain antibody (sc-Ab). Further disclosed are methods and compositions for testing and using the molecules.