Abstract: The invention provides methods for identifying peptide epitopes that activate CD4+ T cells involved in the pathogenesis of diseases, e.g., autoimmune diseases, susceptibility to which is determined by expression of particular class II MHC genes. The invention includes peptides derived from the IA-2 polypeptide by such a method, altered peptide ligands, and methods of therapy involving the use of altered peptide ligands.

Abstract: The present invention is directed to a novel product and method for isolating ectoparasite saliva proteins, and a novel product and method for detecting and/or treating allergic dermatitis in an animal. The present invention includes a saliva protein collection apparatus capable of collecting ectoparasite saliva proteins substantially free of contaminating material. The present invention also relates to ectoparasite saliva proteins, nucleic acid molecules having sequences that encode such proteins, and antibodies raised against such proteins. The present invention also includes methods to obtain such proteins and to use such proteins to identify animals susceptible to or having allergic dermatitis. The present invention also includes therapeutic compositions comprising such proteins and their use to treat animals susceptible to or having allergic dermatitis.

Abstract: The present invention provides isolated peptides of Lol p V, a major protein allergen of the species Lolium perenne. Therapeutic peptides within the scope of the invention comprise at least one T cell epitope, or preferably at least two T cell epitopes of a protein allergen of Lol p V. Diagnostic peptides within the scope of the invention bind IgE. The invention also provides modified peptides having similar or enhanced therapeutic properties or other desirable properties as the corresponding, naturally-occurring allergen or portion thereof. The invention further provides nucleic acid sequences coding for peptides of the invention. Use of the therapeutic compositions comprising one or more peptides of the invention in the manufacture of medicaments for treating sensitivity to Lol p V or an allergen immunologically related to Lol p V, or for general ryegrass sensitivity in an individual, is also provided.

Abstract: The present invention is drawn to an immunogen derived from a protein allergen, which is a) a non-anaphylactic immunogenic recombinant fragment of the protein allergen which contains an IgG epitope partly but not wholly overlapping an IgE epitope of the protein allergen; b) a polymeric form of the fragment, in which the fragment constitutes the monomeric units; or c) a non-anaphylactic recombinant polymeric form of the protein allergen having 2–10 monomeric units, in which the protein allergen constitutes the monomeric units. The present invention is further drawn to the use of the immunogen for in vitro diagnoses of type I allergy and hyposensitization.

Abstract: This invention provides combinations of a tolerance-inducing antigen such as insulin and a mucosal binding component that preferably binds ganglioside GM1. The components are present in a non-covalent arrangement. When administered to a mucosal surface, the combinations are effective in inducing specific immunological tolerance at a 10-fold lower dose than antigen alone. Tolerance is sustained for a number of weeks without the necessity of booster administrations. The compositions and procedures of this invention are of benefit for the prevention or amelioration of conditions attributable to an unwanted immunological response.

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 in general to methods and products for initiating an immune response against an antigen, and in particular relates to transepithelial delivery of antigens to provoke tolerance and immunity. The present invention further relates to methods and products for the transepithelial delivery of therapeutics. In particular, the invention relates to methods and compositions for the delivery of therapeutics conjugated to a FcRn binding partner to intestinal epithelium, mucosal epithelium and epithelium of the lung. The present invention further relates to the synthesis, preparation and use of the FcRn binding partner conjugates as, or in, pharmaceutical compositions for oral systemic delivery of drugs and vaccines.

Abstract: A method of treating spontaneous and ongoing auto-immune diseases in mammals, comprising administering to a mammal, in need of such a treatment, a therapeutically effective amount of one or more non mitogenic anti-CD3 active principles to achieve permanent disease remission through the induction of antigen-specific unresponsiveness, i.e. immune tolerance.

Abstract: Hypoallergenic variants of the major allergen Ph1 p 1 of Phleum pratense plants and their use in the therapy of the allergic diseases is disclosed.

Abstract: Peptide-like compounds and their variants having immunomodulating activity including the N-terminal acylated and/or C-terminal amidated or esterified forms thereof of up to 60 amino acids wherein the peptide-type compound comprises the formula: ??? wherein: ? and ? are the same or different and are of the formula: {R aa76-77 L}(aa79-84)(SEQ ID NO:1) ??(a) or (aa84-79){L aa77-76 R}(SEQ ID NO:2) ??(b) wherein: aa76 is E or V; aa77 is D, S or N; aa79 is R or G; aa80 is I or N; aa81 is a hydrophobic or small amino acid; aa82 is R or L; aa83 is G or R; aa84 is a hydrophobic or small amino acid; wherein the sequence in the brackets may optionally be absent or truncated at any peptide type bond within the brackets may be used by themselves or in combination with immunosuppressant drugs, to reduce CTL activation, particularly in association with transplantation.

Abstract: The invention concerns human monoclonal antibodies to the islet cell antigen IA-2, a process for their production, the use of human monoclonal antibodies in a method for detecting antibodies to IA-2, a method for detecting antibodies to the islet cell antigen IA-2 and a method for detecting the islet cell antigen IA-2 in a sample.

Abstract: The invention concerns a method for preparing Ig fractions from human polyvalent intravenous Immunoglobulins (IV Ig) which are in particular likely to be responsible for the immunomodulatory effect observed during the treatment of certain autoimmune diseases. The invention concerns Ig fractions having reactivity to IgM, IgG F(ab?)2 or DNP hapten and no or little reactivity to non-self antigens, that is Ig fractions which have idiotypic interactions among themselves (connected fraction) or which include natural antibodies reacting with the DNP hapten. Said fractions exhibit a polyreactivity to specific autoantigens.

Abstract: A process for preparing a patient-specific immunoadsorber, which comprises (i) extracting a body fluid from a patient having an immunopathological condition, the fluid containing immune complexes that are relevant to that immunopathological condition, (ii) contacting the extracted fluid with an adsorbent for the immune complexes to form adsorbed immune complexes, (iii) eluting the adsorbed complexes to form an eluate, (iv) fractionating the eluate into a plurality of immune complex component fractions, and (v) immobilizing the immune complex components on one or more biologically compatible carriers activated to bond to its surface one or more desired immune complex components.

Abstract: The subject invention pertains to matrix metalloproteinase (MMP) inhibitors that exhibit an IC50 of below 10−4M against MMP and have substantially no activity against non-MMP metalloproteinase-related events. The MMP inhibitors of the invention have reduced side-effects, especially with respect to joint pain.

Abstract: Variants of allergens of Dermatophagoides pteronyssinus species with reduced allergenic activity.

Abstract: This invention relates to allergenic proteins of natural rubber latex in substantially purified form, their production and their use, together with monoclonal antibodies developed against those allergenic proteins, in assays for the qualitative and quantitative determination of the levels of the allergenic proteins in natural rubber latex or in products made from latex. Assays for identifying and/or quantitating antibodies in blood or blood products that mediate the occurrence of an allergic reaction induced by natural rubber latex are also provided, together with in vivo and in vitro diagnostic tests for detecting hypersensitivity to natural rubber latex and which involve use of the aforesaid allergenic proteins. The invention also provides for the use of the aforesaid allergens as de-sensitizing agents in the treatment of latex protein allergy. There is still further provided a method for removing allergenic proteins from latex products.

Abstract: The present invention is directed to a method of blocking the cytotoxic activity of Fc&ggr;RIII receptor-positive immune cells in a patient with amyotrophic lateral sclerosis using an effective amount of soluble Fc&ggr;RIII receptors. The soluble Fc&ggr;RIII receptors of the invention are specific for immunoglobulin G of under-class 1 (IgG1) and/or 3 (IgG3).

Abstract: Activated immunoglobulin which is useful as an eosinophilia-suppressing agent, immunomodulating agent, therapeutic agent for autoimmune diseases, anfiinflammatory agent and antiallergic agent is obtained by admixing immunoglobulin with a histamine component and then substantially or completely removing the histamine component. The histamine component may be removed or separated by dialysis, gel filtration, adsorption chromatography, ion exchange chromatography, or affinity chromatography. The method imparts pharmacological activity which is not inherently available in immunoglobulin of the natural type to immunoglobulin. The activated immunoglobulin of the present invention has an immunomodulating action which is clearly different from that of conventional immunosuppressive agents.

Abstract: The present invention provides peptide compositions capable of binding glycoproteins encoded by HLA, HLA-B, and HLA-C alleles and inducing T cell activation in T cells restricted by the HLA allele. The peptides are useful to elicit an immune response against a desired antigen.

Abstract: The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.

Abstract: Compositions for stabilizing polypeptides or antigens are described. These compositions are useful for stabilizing polypeptides or antigens stored in aqueous formulations. Such formulations can be used for various analytical or other methods.

Abstract: In the present invention, pharmaceutical compositions containing a histamine-added gamma-globulin as an effective component are used as an immunomodulating agent, a suppressive agent for eosinophilia, and as an antiinflammatory agent. The immunomodulating action is unexpectedly different from the action of conventional immunosuppressive agents. Accordingly, the compositions are useful as a pharmaceutical agent for the therapy of diseases associated with an abnormal immune system such as chronic articular rheumatism, systemic lupus erythematosus, multiple sclerosis, etc. and various types of immunodeficiency syndromes. In addition, the pharmaceutical compositions exhibit suppressive action upon hypereosinophilicity. They may be used as a therapeutic agent for infectious diseases, parasitic diseases, respiratory diseases, autoimmune diseases and eosinophilia caused by malignant tumors. The compositions are excellent antiinflammatory agents.

Abstract: The OX-40 antigen is characterized and claimed together with variants and derivatives thereof. Also described are binding agents for the antigen and the use of these in diagnosis and therapy. Examples of such use include a method for the selective depletion of activated CD4+ T-cells in vivo by using immunotoxins comprising an 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+ T-cells which have been implicated in diseases including Multiple Sclerosis, Rheumatoid Arthritis, Sarcoidosis, and Autoimmune Uveitis as well as inflammatory bowel disease and graft-versus-host disease. This type of therapy is also beneficial for eradicating CD4+ T-cell lymphomas and alloreactive CD4+ 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: Methods for assessing immunocompetence, cellular or humoral immunity, antigen exposure, or allergic conditions in an individual by accelerating diagnostic particles into a target skin site in the individual are provided.

Abstract: The invention relates to the treatment of individuals suffering from a disease associated with leukocyte recruitment to the gastrointestinal tract or other tissues as a result of binding of leukocytes to gut-associated endothelium expressing the molecule MAdCAM (such as inflammatory bowel disease), comprising administering to the individual an effective amount of an antibody which inhibits the binding of leukocytes to endothelial MAdCAM.

Abstract: A chimeric protein comprising a Pseudomonas aeruginosa exotoxin (PE) moiety linked to a myelin basic protein (MBP) moiety is disclosed. The MBP moiety is selected from the group comprising: (a) MBP; (b) amino acids 69-88 of guinea-pig myelin basic protein or an antigenic portion thereof; (c) amino acids 84-102 of human myelin basic protein or an antigenic portion thereof; (d) amino acids 143-168 of human myelin basic protein or an antigenic portion thereof; and (e) an amino acid sequence in which one or more amino acids have been deleted, added, substituted or mutated in the amino acid sequences of (a), (b), (c) or (d), the modified sequence of (e) retaining at least 75% homology with the amino acid sequences of (a), (b), (c) or (d), respectively. Each of the MBP moieties of (b), (c) and (d) are linked to the PE moiety by a pentapeptide linker repeated 1-3 times. The chimeric protein is useful in treating autoimmune diseases, and especially multiple sclerosis.

Abstract: Proinsulin peptide compounds that modulate an immunological response by T cells of Type I diabetic subjects are disclosed. The proinsulin peptide compounds of the invention are preferably derived from a region of proinsulin that spans the junction between the B chain and C peptide of proinsulin. Pharmaceutical compositions comprising the proinsulin peptide compounds are also disclosed. An immunological response to a proinsulin peptide compound of the invention can be used as an indicator of Type I diabetes in a subject. Accordingly, the invention provides diagnostic assays for Type I diabetes using the proinsulin peptide compounds. Methods for inhibiting the development or progression of Type I diabetes in a subject by administering a proinsulin peptide compound are also disclosed.

Abstract: Provided are methods for treating inflammatory diseases in a patient comprising administering to the patient an effective amount of a conjugate consisting essentially of one or more antibody fragments covalently attached to one or more nonproteinaceous polymer molecules, wherein at least one antibody fragment comprises an antigen binding site that binds to human IL-8, and wherein the apparent size of the conjugate is at least about 500 kD.

Abstract: The present invention provides peptide compositions capable of binding glycoproteins encoded by HLA, HLA-B, and HLA-C alleles and inducing T cell activation in T cells restricted by the HLA allele. The peptides are useful to elicit an immune response against a desired antigen.

Abstract: Fusion polypeptides and salts thereof comprising at least one IgE-binding domain fused to at least one human serum albumin component, optionally via a peptide linker, and in particular, dimeric fusion polypeptides comprising HSA protein fused, at each of its amino and carboxy termini, to an extracellular domain of the &agr;-chain of the human high affinity receptor for IgE (Fc&egr;RI&agr;); process for the preparation thereof, functionally equivalent polypeptides which are intermediates in their preparation, and polynucleotide and oligonucleotide intermediates and vectors therefor. They are indicated for use in the prevention and/or treatment of IgE-mediated allergic diseases and related disorders such as atopic dermatitis, atopic asthma and chronic urticaria.

Abstract: Isolated nucleic acids encoding allergens of the species Dermatophagoides pteronyssinus and Dermatophagoides farinae, Der p VII and Der f VII, respectively, are disclosed. A cDNA encoding a peptide having a Der p VII activity and a predicted molecular weight of about 22, 177 daltons is described. A cDNA encoding a peptide having Der f VII activity is also described. The nucleic acids of the invention can be used as probes to detect the presence of Der p VII or Der f VII nucleic acid in a sample or for the recombinant production of peptides having a Der p VII or Der f VII activity. Peptides having a Der p VII or Der f VII activity can be used in compositions suitable for pharmaceutical administration or methods of diagnosing sensitivity to house dust mite allergens.

Abstract: The present invention is based on peptide binding specificities of HLA DR4w4, DR1 and DR7. Peptides binding to these DR molecules have a motif characterized by a large aromatic or hydrophobic residue in position 1 (Y, F, W, L, I, V, M) and a small, non charged residue in position 6 (S, T, C, A, P, V, I, L, M). In addition, allele-specific secondary effects and secondary anchors are defined, and these results were utilized to derive allele specific algorithms. By the combined use of such algorithms peptides capable of degenerate DR1, 4, 7 binding were identified.

Abstract: The present invention relates to a counter-receptor, termed CD40CR, for the CD40 B-cell antigen, and to soluble ligands for this receptor, including fusion molecules comprising at least a portion of CD40 protein. It is based, at least in part, on the discovery that a soluble CD40/immunoglobulin fusion protein or antibody specific for gp39 on T cells was able to inhibit helper T-cell mediated B-cell activation by binding to a novel 39 kD protein receptor on helper T-cell membranes. The present invention provides for a substantially purified CD40CR receptor; for soluble ligands of CD40CR, including antibodies as well as fusion molecules comprising at least a portion of CD40 protein; and for methods of controlling B-cell activation which may be especially useful in the treatment of allergy or autoimmune disease, including graft-versus-host disease and rheumatoid arthritis.

Abstract: An agent comprising a mucosa-binding molecule linked to a specific microbial antigen is disclosed. Further, a method of inducing immnunological tolerance in an individual against a specific microbial antigen, including hapten, which causes an unwanted immune response in said individual, comprising administration by a mucosal route of an immunologically effective amount of an immunological tolerance-inducing agent of the invention to said individual, is described.

Abstract: The prevention and treatment of autoimmune disease in humans (as well as other animals) is described through the use of ligands directed to cytokines. Antibodies and receptors to the proinflammatory cytokines IL-2, TNF, IL-12 and IFN-gamma are employed (along with other ligands to such cytokines). Such ligands administered luminally are effective (as demonstrated in two experimental models of autoimmune disease) at delaying the onset of autoimune disease.

Abstract: An immunological tolerance-inducing agent comprising a mucosa-binding molecule linked to a specific tolerogen is disclosed. Further, a method of inducing immunological tolerance in an individual against a specific antigen, including hapten, which causes an unwanted immune response in said individual comprising administration by a mucosal route of an immunologically effective amount of an immunological tolerance-inducing agent of the invention to said individual, is described.

Abstract: A pharmaceutical kit and process useful for achieving prolonged immunosuppression and tumor cell elimination, wherein the kit comprises a first antibody having binding specificity for T cells and is capable of eliminating T cells in vivo; and a second antibody, having binding specificity for T cells and is capable of eliminating T cells in vivo, capable of modulating the antigen effect of T cells or both, wherein said first antibody differs from said second antibody in the constant region of its heavy chains and thus belongs to a different animal species, wherein said first antibody and said second antibody are maintained separately in said kit, and wherein in said process said first antibody is first applied once or several times and said second antibody is applied at a different time from said first antibody.

Abstract: There is disclosed the use, as an agent in the treatment or the prevention of an autoimmune disease, of: (i) an agent having GM-1 binding activity, other than Ctx or Etx, or the B subunits of Ctx and Etx; or (ii) an agent having an effect on GM-1 mediated intracellular signalling events, but no GM-1 binding activity. These agents may also be used in the treatment of human T cell leukaemia, in the prevention of transplant rejection or GVHD or in a vaccination method for vaccinating a mammalian subject.

Abstract: The present invention relates to a product and process for suppressing an immune response using a T lymphocyte veto molecule capable of blocking cell surface molecules responsible for T cell activation. Disclosed is a CD4 or CD2 molecule, associated with an immunoglobulin molecule capable of binding to a major histocompatibility antigen. Also disclosed is a method to produce a T lymphocyte veto molecule, a therapeutic composition comprising a T lymphocyte veto molecule and methods to use T lymphocyte veto molecules in therapeutic processes requiring suppression of an immune response.

Abstract: The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.

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

Abstract: Methods and antibody compositions are provided for the diagnosis and treatment of lupus nephritis. By employing B-cells of a lupus nephritis host with a fusion partner, antibodies can be obtained, which may serve as immunogens for the production of antiidiotypic antibodies, which may then be used for diagnosis and therapy of lupus nephritis.

Abstract: The subject invention concerns a method for therapeuticaly treating a patient afflicted with autoimmune disorders or disease. The subject method comprises admninistering to a patient an antibody composition that is capable of binding to and inhibiting self-reactive pathogenic anti-bodies present within the patient. Specifically exemplified is a method for treating systemic lupus erythematosis wherein the antibody composition administered to the patient comprises purified anti-DNA anti-idiotypic antibodies. The subject invention further concerns a method for purifying from pooled human gamma globulin preparations anti-idiotype antibodies useful in the present therapeutic method. The present invention further concerns a purified antibody composition useful in the present therapeutic method.

Abstract: A reagent for immunologically detecting rheumatism containing as an antigen at least one mammalian protein selected from among ezrin, radixin and moesin and/or a peptide composed of at least nine consecutive amino acid residues found in the amino acid sequences of ezrin, radixin and moesin; and a method of detecting autoantibodies present in the serum of a rheumatic. An immunological reaction using this reagent enables precritical or early diagnosis of rheumatism. An immunological detection using the above autoantigenic proteins is convenient and reliable as an early serodiagnostic method based on rheumatism-specific antigens.

Abstract: Compounds of general formula (I): have utility as inhibitors of matrix metalloproteinases and TNF.

Abstract: Isolated cDNAs derived from mRNAs expressed in human cells are provided, as are DNAs and RNAs comprising their nucleotide sequences, and vectors for expressing the cDNAs. The cDNAs encode proteins which have functions similar to known proteins.

Abstract: Novel oligopeptides comprising a sequence associated with HLA-B .alpha..sub.1 domain, but comprising a tyrosine-tyrosine-tryptophan triad are provided for use in inhibiting cytotoxic activity of CTLs and natural killer cells. By combining the subject compositions with mixtures of cells comprising the cytotoxic cells and cells which would otherwise activate the cytotoxic cells, lysis of the target cells can be substantially inhibited. The oligopeptides may be joined to a wide variety of other groups or compounds for varying the activity of the subject compositions. The subject compositions may be administered by any convenient means to a host to inhibit CTL and NK attack on tissue, particularly involved with xenogeneic or allogeneic transplants.

Abstract: Uses for Wnt polypeptides in hematopoiesis are disclosed. In particular, in vitro and in vivo methods for enhancing proliferation, differentiation or maintenance of a hematopoietic stem/progenitor cell using a Wnt polypeptide, and optionally another cytokine, are described.

Abstract: An agent comprising a mucosa-binding molecule linked to a specific microbial antigen is disclosed. Further, a method of inducing immunological tolerance in an individual against a specific microbial antigen, including hapten, which causes an unwanted immune response in said individual, comprising administration by a mucosal route of an immunologically effective amount of an immunological tolerance-inducing agent of the invention to said individual, is described.

Abstract: Tripeptidyl derivatives having a SH or acylS group and which are amides, have therapeutic utility via MMP or TNF inhibition.