Abstract: The invention identifies PD-1 as a receptor for B7-4. B7-4 can inhibit immune cell activation upon binding to an inhibitory receptor on an immune cell. Accordingly, the invention provides agents for modulating PD-1, B7-4, and the interaction between B7-4 and PD-1 in order to modulate a costimulatory or an inhibitory signal in a immune cell resulting in modulation of the immune response.

Abstract: The present invention provides for crystalline cPLA2. The crystal structure of cPLA2 has also been solved using such material. Models based upon such crystal structure are also provided. Methods of identifying inhibitors of cPLA2 activity and membrane binding using such models are also disclosed.

Abstract: The present invention provides therapeutic compositions and methods for treating disease conditions in humans associated with an antigen specific immune response by the human to an antigen such as a protein antigen (i.e. allergy and autoimmune diseases). Therapeutic compositions of the invention are reproducible preparations which are suitable for human therapy. Compositions of the invention comprise at least one isolated peptide having a defined sequence of amino acid residues and the composition is capable of down regulating an antigen specific immune response to an offending antigen in a population of humans subject to the antigen specific immune response. Compositions and methods of the invention may be used to treat sensitivity to protein allergens in humans and may also be used to treat autoimmune disease such as rheumatoid arthritis, diabetes, myasthenia gravis, Grave's disease, Good Pasture's syndrome, thyroiditis and multiple sclerosis.

Abstract: Isolated nucleic acids encoding an allergen of Dermatophagoides pteronyssinus, Der p III, are disclosed. A cDNA encoding a peptide having a Der p III activity and a predicted molecular weight of about 24,985 daltons is also described. The nucleic acids can be used as probes to detect the presence of Der p III nucleic acid in a sample or for the recombinant production of peptides having an activity of Der p III. Peptides having an activity of Der p III can be used in compositions suitable for pharmaceutical administration or methods of diagnosing sensitivity to house dust mites.

Abstract: CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g.

Abstract: Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific. T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed.

Abstract: Isolated DNA encoding allergens of Dermatophagoides (house dust mites) particularly of the species Dermatophagoides farinae and Dermatophagoides pteronyssinus, which are protein allergens or peptides which include at least one epitope of the protein allergen. In particular, DNA encoding two major D. farinae allergens, Der f I and Der f II and DNA encoding a D. pteronyssinus allergen, Der p I. In addition, the proteins or peptides encoded by the isolated DNA, their use as diagnostic and therapeutic reagents and methods of diagnosing and treating sensitivity to house dust mite allergens.

Abstract: Methods for modulating T cell responses by manipulating intracellular signals associated with T cell costimulation are disclosed. The methods involve inhibiting or stimulating the production of at least one D3-phosphoinositide in a T cell. Production of D3-phosphoinositides can be manipulated by contacting a T cell with an inhibitor or activator of phosphatidylinositol 3-kinase. Inhibitors of phosphatidylinositol 3-kinase for use in the methods of the invention include wortmannin and quercetin, or derivatives or analogues thereof. The methods of the invention can further comprise modulating other intracellular signals associated with costimulation, such as protein tyrosine phosphorylation, for example by modulating the activity of a protein tyrosine kinase or a protein tyrosine phosphatase in the T cell.

Abstract: Novel structural forms of T cell costimulatory molecules are described. These structural forms comprise a novel structural domain or have a structural domain deleted or added. The structural forms correspond to naturally-occurring alternatively spliced forms of T cell costimulatory molecules or variants thereof which can be produced by standard recombinant DNA techniques. In one embodiment, the T cell costimulatory molecule of the invention contains a novel cytoplasmic domain. In another embodiment, the T cell costimulatory molecule of the invention contains a novel signal peptide domain or has an immunoglobulin variable region-like domain deleted. The novel structural forms of T cell costimulatory molecules can be used to identify agents which stimulate the expression of alternative forms of costimulatory molecules and to identify components of the signal transduction pathway which results in costimulation of T cells.

Abstract: Disclosed is a composition for inhibiting the interactions of B7-1 and B7-2 with their natural ligands. Such compositions comprise an antibody specific for B7-2 and an antibody specific for B7-1, in a pharmaceutically acceptable carrier. The composition may be formulated for either separate or combined administration of the antibody components. The antibodies may be monoclonal antibodies, or humanized antibodies. Preferred antibodies are disclosed.

Abstract: The present invention provides for the use of G protein binding agents for prophylactic and/or therapeutic treatment of septic shock. The present invention provides methods of using agents which bind G protein to treat a subject having or susceptible to septic shock. The present invention further pertains to compositions for treating a subject for septic shock. The composition includes an effective amount of a G protein binding agent such as mastoparan and, optionally, an antibiotic and a pharmaceutically acceptable carrier. Other aspects of the invention include packaged agents which bind G proteins for treating septic shock.

Abstract: The invention provides isolated nucleic acids molecules, designated GL50 nucleic acid molecules, which encode GL50 polypeptides. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing GL50 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a GL50 gene has been introduced or disrupted. The invention still further provides isolated GL50 polypeptides, fusion proteins, antigenic peptides and anti-GL50 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: The invention provides isolated nucleic acids molecules, designated DHDR nucleic acid molecules, which encode novel DHDR-related dehydrogenase molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing DHDR nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a DHDR gene has been introduced or disrupted. The invention still further provides isolated DHDR proteins, fusion proteins, antigenic peptides and anti-DHDR antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

Abstract: Porcine cardiomyocytes and methods for using the cardiomyocytes to treat disorders characterized by insufficient cardiac function are described. The porcine cardiomyocytes are preferably embryonic porcine cardiomyocytes. The porcine cardiomyocytes can be modified to be suitable for transplantation into a xenogeneic subject, such as a human. For example, the porcine cardiomyocytes can be modified such that an antigen (e.g., an MHC class I antigen) on the cardiomyocyte surface which is capable of stimulating an immune response against the cardiomyocytes in a xenogeneic subject is altered (e.g., by contact with an anti-MHC class I antibody, or a fragment or derivative thereof) to inhibit rejection of the cardiomyocyte when introduced into the subject. In one embodiment, the porcine cardiomyocytes are obtained from a pig which is essentially free from organisms or substances which are capable of transmitting infection or disease to the recipient subject.

Abstract: The present invention relates to BCL-x&ggr;, a novel isoform of the BCL-x family of proteins which is predominantly expressed in T-lymphocytes and is associated with resistance to apoptosis. Both compositions of matter and methods are described which are useful in the treatment or prevention of immune system disorders.

Abstract: The present invention provides for crystalline GFS. The crystal structure of GFS has also been solved using such material. Models based upon such crystal structure are also provided. Methods of identifying inhibitors of GFS activity using such models are also disclosed.

Abstract: Methods for stimulating a T cell response to a tumor cell in a subject with a tumor which involve modifying the tumor cell to express a CD2 ligand and a CD28 or CTLA4 ligand, are disclosed. Methods wherein the tumor cell is obtained from the subject and modified ex vivo to form a modified tumor cell and then the modified tumor cell is administered to the subject, are also disclosed.

Abstract: CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g.

Abstract: The invention provides isolated nucleic acids molecules, designated PGC-1 nucleic acid molecules, which encode proteins which can modulate various adipocyte-associated activities including, for example, thermogenesis in adipocytes, e.g., brown adipocytes, and adipogenesis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: Highly purified mocarhagin, a cobra venom protease, is disclosed. Pharmaceutical compositions and therapeutic uses of the highly purified protease are also provided. Polynucleotides encoding such protease and related proteases are also disclosed.