Abstract: Novel peptides which are epitopes of the human 60 kDa heat shock protein (hsp60) may be used for the diagnosis and treatment of insulin-dependent diabetes mellitus (IDDM). Pharmaceutical compositions containing such peptides and kits for use in diagnosis of IDDM are also disclosed.

Abstract: The present invention is directed to complexes consisting essentially of an isolated MHC component and an autoantigenic peptide associated with the antigen binding site of the MHC component. These complexes are useful in treating autoimmune disease.

Abstract: The present invention relates to the diagnosis of severe diseases based on the determination of the presence of AGE-IgG autoantibodies in patients and to a method of treatment thereof. More precisely, the invention relates to a method for the diagnosis of severe diseases in patients, which comprises the steps of: a) incubating a solid support coated with an AGE antibody with a biological sample from said patient for a time sufficient for an immunoreaction to occur; and b) determining the presence of AGE-IgG autoantibodies present in said sample; whereby the presence of AGE-IgG autoantibodies in said patient's sample is indicative of a severe disease. Such severe diseases which may be diagnosed in accordance with the present invention include Rheumatoid arthritis, atherosclerosis, amyloidosis, diabetes, Henoch Schonlein Purpura, Crohn's disease and Coeliac disease.

Abstract: The present invention relates to a heterofunctional cellular immunological reagent comprising at least two T cell specific binding ligands covalently linked together, wherein one of the T cell specific binding ligands binds to a specific class or subclass of T cells and another of the T cell specific binding ligands is an antigen associated with disease or a causative agent of disease, or epitope thereof. The present invention also relates to vaccines containing the heterofunctional cellular immunological reagents and methods for the use of the same.

Abstract: Pooled human immunoglobulin may be administered orally to rheumatoid arthritis patients to treat the rheumatoid arthritic condition of those patients. Oral administration of pooled human immunoglobulin can result in significant clinical improvement in the level of disease activity in patients with rheumatoid arthritis.

Abstract: The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens completed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific .beta.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders. For example, genes which are differentially expressed within and among T helper (TH) cells and TH cell subpopulations, which include, but are not limited to TH0, TH1 and TH2 cell subpopulations are identified. Genes are also identified via the ability of their gene products to interact with gene products involved in the differentiation, maintenance and effector function of such TH cells and TH cell subpopulations. The genes identified can be used diagnostically or as targets for therapeutic intervention. In this regard, the present invention provides methods for the identification and therapeutic use of compounds as treatments of immune disorders, especially TH cell subpopulation-related disorders.

Abstract: The invention describes peptides derived from tumor rejection antigen precursor MAGE-2. These peptides bind with HLA-A2 molecules, thus presenting complexes which provoke cytolytic T cell production. The resulting "CTLs" are specific for complexes of HLA-A2 and the peptide. The complexes can be used to generate monoclonal antibodies. The cytolytic T cells produced may be used in the context of immunotherapy, such as adoptive transfer.

Abstract: This invention provides analogs of L-Glu-L-Trp and methods of using them for immunomodulation and treatment of pathological neovascular conditions. The analogs include the substitution of a carbon atom for a nitrogen atom in the indole ring of tryptophan.

Abstract: Chimeric MHC Class I molecules having a recipient-type N-terminus, a donor-type alpha-1 helical region, and a recipient-type alpha-2 domain induce tolerance to donor grafts when administered to the recipient at time of transplantation.

Abstract: Peptidyl compounds having an imidazole substituent have therapeutic utility via their inhibitory effect on metalloproteinases and tumour necrosis factor.

Abstract: The present invention provides a method and products for establishing nutrient recognition and improving nutrient utilization and growth in a human or an animal by immunologically stimulating digestion or a gastric cascade within the gastrointestinal tract, by orally or parenterally immunizing the human or animal with an immunizing effective amount of an ingestible antigen or a mixture of ingestible antigens and orally reintroducing the antigen(s). Another aspect of the invention provides a method and products for preventing and treating gastrointestinal disease by immunologically stimulating a gastric cascade, namely, blood flow, production of mucus and release of digestion regulatory factors within the gastrointestinal tract of a human or an animal, by orally or parenterally immunizing the human or the animal with an immunizing effective amount of an ingestible antigen or a mixture of ingestible antigens and orally reintroducing the antigen(s).

Abstract: The invention provides a new method for antiglobulin testing from serum of a potential blood transfusion recipient in which warm autoantibodies are removed from serum so as to allow identification of alloantibodies present. The method involves contacting serum from a patient with one or more ligands that bind warm autoantibodies but do not bind alloantibodies, separating the non-bound serum components from the bound warm autoantibodies, and using the warm autoantibody-depleted serum in antiglobulin testing. Suitable ligands include phospholipids, the polar head groups of phosphoglycerides, and naturally occurring and synthetic analogues of these molecules.

Abstract: The present invention relates to a method for the treatment of multiple sclerosis comprising administering to a patient an antibody which binds to neurotactin. Neurotactin is a membrane-anchored chemokine which is highly expressed in normal mammalian brain.

Abstract: The invention relates to methods and compositions for the treatment of autoimmune disease. Specifically, compositions comprising heat shock proteins, including gp96, hsp90, and hsp70, are disclosed. Immunotherapeutic methods for administering the hsp-containing compositions are disclosed. Furthermore, methods for preventing rejection of organs transplanted to treat autoimmune disease are disclosed. The disclosed methods are useful for treating a variety of autoimmune diseases, including insulin dependent diabetes mellitus.

Abstract: Compositions and methods for the treatment or prevention of insulin dependent diabetes (IDD) are provided. Specifically, glutamic acid decarboxylase (GAD) proteins, and fragments. thereof, can be administered to an animal in order to the reduce the severity of IDD.

Abstract: Dipeptidyl derivatives having a SH of acylS group and which are amides, thioamides or S(O).sub.0-2 -amides, have therapeutic utility via MMP or TNF inhibition.

Abstract: The present invention relates to a method for adjusting the affinity of a polypeptide to a target molecule by a combination of steps, including: (1) the identification of aspartyl residues which are prone to isomerization; (2) the substitution of alternative residues and screening the resulting mutants for affinity against the target molecule. In a preferred embodiment, the method of subtituting residues is affinity maturation with phage display (AMPD). In a further preferred embodiment the polypeptide is an antibody and the target molecule is an antigen. In a further preferred embodiment, the antibody is anti-IgE and the target molecule is IgE. In another embodiment, the invention relates to an anti-IgE antibody having improved affinity to IgE.

Abstract: A general method for vaccinating against any pathogen is presented. The method utilizes expression library immunization, where an animal is inoculated with an expression library constructed from fragmented genomic DNA of the pathogen. All potential epitopes of the pathogen's proteins are encoded in its DNA, and genetic immunization is used to directly introduce one or more expression library clones to the immune system, producing an immune response to the encoded protein. Inoculation of expression libraries representing portions of the Mycoplasma pulmonis genome was shown to protect mice from subsequent challenge by this natural pathogen. Protection against Listeria.

Abstract: Peptidyl compounds have therapeutic utility via MMP/TNF inhibition.

Abstract: The invention identifies the CTLA4 receptor as a ligand for the B7 antigen. The complete amino acid sequence encoding human CTLA4 receptor gene is provided. Methods are provided for expressing CTLA4 as an immunoglobulin fusion protein, for preparing hybrid CTLA4 fusion proteins, and for using the soluble fusion proteins, fragments and derivatives thereof, including monoclonal antibodies reactive with B7 and CTLA4, to regulate T cell interactions and immune responses mediated by such interactions.

Abstract: Peanuts are a common cause of food hypersensitivity reactions. The sera of 10 patients who had atopic dermatitis and a positive double-blind placebo-controlled food challenge to peanut were used to investigate the major allergens of peanut. Crude Florunner extracts were fractionated by anion-exchange chromatography using a step gradient (limit buffer, 0.05M BisTris/1.5M NaCl). One hundred microliters of each 2.0 ml fraction was dot-blotted onto nitrocellulose paper and IgE-binding activity assessed using the serum pool to select allergen-containing fractions. A protein peak (OD 280) which eluted at 10% NaCl and demonstrated intense IgE-binding was further analyzed by two-dimensional SDS-PAGE/immunoblot analysis. The majority of this fraction is a protein which has a molecular weight of 17 kD and a pI of 5.2. Sequencing data from the N-terminus revealed the following initial 9 amino acids: (*)-Q-Q-(*)-E-L-Q-D-L.

Abstract: This invention discloses a method for the treatment or prevention of autoimmune diseases, allergic or atopic disorders and graft rejection. Specifically, it provides a means of killing a specific sub-population of T lymphocytes while leaving the majority of other T lymphocytes in the population unaffected. The sub-population of T lymphocytes are killed by repeatedly challenging the population with an antigen in conjunction with administration of interleukin-4.

Abstract: The invention provides novel methods and compositions for the treatment of immune system-mediated arthritis, including rheumatoid arthritis. The subject compositions comprise one or more different types of collagen or collagen derivatives and a mucosa binding structure. Specific combinations of collagen and/or collagen derivatives may be used to treat specific types of arthritis. The collagen(s) and/or collagen(s) derivatives used in the subject compositions may be either obtained from natural sources or produced by recombinant genetic engineering techniques by chemical modification. Another aspect of the invention is to provide methods for treating various types of arthritis by administering an effective amount of the subject collagen-containing compositions. The methods of the invention involve the oral administration of a collagen or collagens found in a specific tissue, e.g.

Abstract: The present invention relates to a novel polypeptide which has secretion enhancing activity on lacrimal and parotid gland cells, monoclonal antibodies thereto, and methods of diagnosising Sjorgren's syndrome using these antibodies.

Abstract: The present invention describes the application of specifically derived stress proteins in the modulation of certain specific immune responses in the human and animal body. This application under certain conditions may require the in vitro (out of body) treatment of certain tissues (including cells of all lineages) derived from the intended recipient body or specific donor body, in the case of organ or cell transplantation. The intracellular activity and the subsequent protection against mortality in a cell or tissue has been described in another U.S. patent, U.S. Pat. No. 5,348,945 entitled "Method of treatment with HSP70". The present invention differs from the aforementioned patent in that it does not describe a method for non-specific or specific protection against mortality. The invention may be employed to suppress allograft rejection and the rejection of xenografts, transplanted into human and/or animals.

Abstract: Fragments from the polymorphic domains of Class I HLA antigen domains are used to modulate T-cell activity. The peptides are from the .alpha.1- or .alpha.2 domains, particularly of the HLA-A, and B antigens. The peptides may be conjugated to other compounds to be used in diagnosis and therapy. The peptides may block lysis, CTL proliferation or have other regulating effects.

Abstract: The invention identifies the CTLA4 receptor as a ligand for the B7 antigen. The complete amino acid sequence encoding human CTLA4 receptor gene is provided. Methods are provided for expressing CTLA4 as an immunoglobulin fusion protein, for preparing hybrid CTLA4 fusion proteins, and for using the soluble fusion proteins, fragments and derivatives thereof, including monoclonal antibodies reactive with B7 and CTLA4, to regulate T cell interactions and immune responses mediated by such interactions.

Abstract: An immune suppressive product prepared by injecting an allergen or a mixture of allergens into the body of milk-producing species. Said product being the milk or a polypeptide subfraction of milk obtained from the allergen treated host. The immune suppressive product(s) is milk and or the polypeptide fractions contained therein, which is ostensively free of the intact allergen or allergens used for the treatment of the host. The immune suppressive factor(s) being a subfraction of the allergen used for the treatment. A method of preparing immune suppressive polypeptides from intact allergens, which involves injection of the specific intact allergens into a milk-producing species, collecting the immune suppressive polypeptide fractions of the intact allergens from the milk of the treated host. The immune suppressive milk containing said polypeptide fractions, and/or the polypeptide fractions obtained from said milk, are nonreactive in animals and humans as allergens.

Abstract: Substances comprising disaccharides and substances comprising carboxylated and/or sulfated oligosaccharides in substantially purified form, and methods of using same, are disclosed for the regulation of cytokine activity in a host. For instance, the secretion of active Tumor Necrosis Factor Alpha (TNF-.alpha.) can be either inhibited or augmented selectively by administration to the host of an effective amount of a substance of the invention. Thus, the present invention also relates to pharmaceutical compositions and their use for the prevention and/or treatment of pathological processes involving the induction of active cytokine secretion, such as TNF-.alpha.. The invention also relates to the initiation of a desirable immune system-related response by the host to the presence of activators, including pathogens. The substances and pharmaceutical compositions of the present invention may be administered daily, at very low effective doses, typically below 0.

Abstract: The present invention concerns novel mercaptoalkylpeptidyl compounds of formula (I) which are useful inhibitors of matrix metalloproteinase and/or TNF-mediated diseases including degenerative diseases and certain cancers. The invention also concerns methods of treating patients suffering from disorders or diseases which can be attributed to or are associated with matrix metalloproteinase or TNF activity.

Abstract: The present invention concerns TCR ligands with immunomodulatory properties, as well as methods of identifying such ligands and of using such ligands to modulate T cell effector responses.

Abstract: The present invention provides vaccines and a means of vaccinating a mammal so as to prevent or control specific T cell mediated pathologies or to treat the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the mammal in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides a specific .beta.-chain variable region of the T cell receptor, designated V.beta.17, which is central to the pathogenesis of rheumatoid arthritis (RA).

Abstract: The present invention is directed to methods of suppressing inflammatory responses, inducing tolerance to an antigen, and suppressing cell adhesion, e.g., involved in metastasis, by the administration of lectin derived carbohydrate binding peptides or derivatives thereof, in particular, peptides capable of binding terminally linked .alpha.-sialic acid(2.fwdarw.6).beta.Gal- and/or .alpha.-sialic acid(2.fwdarw.3).beta.Gal-groups on structures or molecules comprising such groups. Pharmaceutical compositions containing such lectin derived carbohydrate binding peptides or derivatives thereof are also disclosed.

Abstract: Inflammation can be treated or prevented altogether by administering a preparation comprising IgA. These preparations also can effect immunomodulation. Preferably, the preparation includes multimeric IgA and is essentially free of IgG in its various forms. Other compounds, such as antibiotics, antiphlogistic agents and antacids, also may be administered. Immunoglobulin A may also be used in vaccines to prevent inflammation. Additionally, an improved assay for evaluating anti-inflammatory activity is provided.

Abstract: Human P450 IID6 cytochrome-derived peptide fragments, anti peptide anti fragment antibodies and applications thereof in the diagnosis of autoimmune hepatitis and more especially in the differential diagnosis between autoimmune hepatitis and other chronic viral forms of hepatitis, such as hepatitis C or B. Said human P450 cytochrome peptide fragment contains at least one P450 IID6 cytochrome immunodominant epitope and consists of an amino acid sequence comprising from 3 to 70 amino acids. Said peptide binds specifically with anti-LKM auto-anitbodies produced in autoimmune hepatitis.

Abstract: An immune suppressive product prepared by injecting an allergen or a mixture of allergens into the body of milk-producing species. Said product being the milk or a polypeptide subfraction of milk obtained from the allergen treated host. The immune suppressive product(s) is milk and or the polypeptide fractions contained therein, which is ostensively free of the intact allergen or allergens used for the treatment of the host. The immune suppressive factor(s) being a subfraction of the allergen used for the treatment. A method of preparing immune suppressive polypeptides from intact allergens, which involves injection of the specific intact allergens into a milk-producing species, collecting the immune suppressive polypeptide fractions of the intact allergens from the milk of the treated host. The immune suppressive milk containing said polypeptide fractions, and/or the polypeptide fractions obtained from said milk, are nonreactive in animals and humans as allergens.

Abstract: A 65 KD heat shock protein, proteins cross-reactive therewith, antibodies thereto or T cells specific thereto can be used for detecting in humans the existence of, a tendency to develop, or the initiation of a process leading to insulin dependent diabetes mellitus. Antibodies to hsp65 can be used to detect the hsp65 molecule in blood or urine. The hsp65 molecule of any species, or any other substance immunologically cross-reactive therewith, when administered with a tolerogenic carrier, can be used for the prevention or treatment of IDDM prior to development of clinical symptoms thereof. T cells, active fragments thereof or the receptor peptide thereof can also be used for prevention or treatment of IDDM.

Abstract: TCR peptides from the V.beta.5 family, particularly those encompassing at least a part of the second complementarity determining region, are useful, e.g., in the diagnosis and treatment of multiple sclerosis.

Abstract: Proteins produced by human lymphocytes are described, particularly a protein which is expressed on their surface. DNA sequences coding these proteins and their pharmaceutical and biological uses are also described.

Abstract: The invention identifies the CTLA4 receptor as a ligand for the B7 antigen. The complete amino acid sequence encoding human CTLA4 receptor gene is provided. Methods are provided for expressing CTLA4 as an immunoglobulin fusion protein, for preparing hybrid CTLA4 fusion proteins, and for using the soluble fusion proteins, fragments and derivatives thereof, including monoclonal antibodies reactive with B7 and CTLA4, to regulate T cell interactions and immune responses mediated by such interactions.

Abstract: The present invention discloses the first peptide sequence of a so called minor H antigen, The minor H antigens are associated with the Graft-versus-Host Disease. The peptide and its derivatives find many uses in bone marrow transplantation, organ transplantation and in the treatment of leukemia. The peptide and its derivatives can be incorporated in vaccines, in pharmaceutical formulations and they can be used in diagnostic test kits. The peptide is derived from the HA-2 minor antigen and has the sequence YXGEVXVSV (SEQ ID NO: 1), wherein X represents a leucine or an isoleucine residue. Both donors and recipients in bone marrow transplantation can be treated with the peptides, optionally in combination with other peptides, coupled to carriers, with suitable excipients and/or adjuvants.

Abstract: A method for the selective depletion of activated CD4.sup.+ T-cells in vivo by using immunotoxins comprising the OX-40 antibody conjugated to a toxic molecule (such as Ricin-A chain). The administration of these specific immunotoxins is used therapeutically to deplete autoimmune reactive CD4.sup.+ T-cells which have been implicated in diseases including Multiple Sclerosis, Rheumatoid Arthritis, Sarcoidosis, and Autoimmune Uveitis. This type of therapy is also beneficial for eradicating CD4.sup.+ T-cell lymphomas and alloreactive CD4.sup.+ T-cells involved with a transplantation reaction. The use of the human form of the OX-40 antibody will also help in the early diagnosis of all the diseases mentioned above.

Abstract: Herein described is an invention of the usage, design and effective procedures 1.) for selected combined methods for preparation and 2.) for coordination of sequence, dosage and administration in utilizing anti-HIV thiophenoyl urea TUR (or related drugs) chemotherapy as well as for utilizing HIV induced or augmented nonvirion antigen NVA (or early polypeptide vaccine EPV or related or derivative) immunotherapy in treatment of HIV+ and AIDS patients (and applicable to Karposi's sarcoma and to other retroviral diseases). Herein described is an invention of 3.

Abstract: A method for increasing the T4/T8 ratio in a human with a depressed T4/T8 ratio comprising administering insulin-like growth factor I (IGF-1) is disclosed.

Abstract: The present invention provides compositions and methods of inhibiting or inducing activation of T cells in a patient. The methods comprise administering a therapeutically effective dose of pharmaceutical compositions comprising a pharmaceutically acceptable carrier and peptides of between about 4 and about 20 residues, that bind antigen binding sites on MHC molecules encoded by substantially all alleles of a DR locus. These peptides are referred to as pan DR binding peptides. The pan DR binding peptides can be used to inhibit immune responses associated with immunopathologies, such as autoimmunity, allograft rejection and allergic responses. The peptides can also be used in combination with CTL peptides to enhance a CTL response.

Abstract: The present invention is directed to complexes comprising an isolated MHC subunit component, an antigenic peptide and, in some cases, an effector component. The antigenic peptide is associated with the antigen binding site of the MHC subunit component. These complexes are useful in treating autoimmune disease.

Abstract: Polypeptides and proteins comprising the CD2-binding domain of LFA-3 are disclosed. DNA sequences that code on expression for those polypeptides and proteins, methods of producing and using those polypeptides and proteins, and therapeutic and diagnostic compositions are also disclosed. Deletion mutants unable to bind CD2 and methods for their use are also disclosed. In addition, fusion proteins which comprise the CD2-binding domain of LFA-3 and a portion of a protein other than LFA-3, DNA sequences encoding those fusion proteins, methods for producing those fusion proteins, and uses of those fusion proteins are disclosed.

Abstract: Fragments from the polymorphic domains of Class I HLA antigen domains are used to modulate T-cell activity. The peptides are from the .alpha.1- or .alpha.2 domains, particularly of the HLA-A, and B antigens. The peptides may be conjugated to other compounds to be used in diagnosis and therapy. The peptides may block lysis, CTL proliferation or have other regulating effects.

Abstract: The present invention comprises the method of selectively suppressing an immune response of a mammal to a particular alloantigen. The method includes several steps. One step is administering to a mammal an effective amount of UVB-radiation. Epidermal cell cultures, when subjected to UVA or UVB irradiation produce specific immunosuppressive factors. This UV-radiation is preferably UVA radiation (320 nm to 400 nm), or UVB-radiation (280 nm to 320 nm). It is demonstrated herein that UVA radiation results in in vitro cells producing a factor which selectively suppresses the CHS response in mammals, while UVB radiation selectively suppresses the DTH response in mammals. Another step of the inventive method involves desensitizing a mammal to a particular alloantigen. It has been determined that a mammal will become tolerant to a particular alloantigen once the subject mammal has been irradiated with a pre-determined wavelength of UVR and thereafter sensitized with the particular alloantigen.