A collaborative study between Johns Hopkins University and ImmuLogic Pharmaceutical Corporation is proposed. The proposal will test in man whether administration of a synthesized peptide of a T cell reactive epitope will alter T cell responsiveness to the epitope. We will also determine whether antibody responses and allergic inflammation to the protein are also altered. In studies of peripheral blood cell cultures from patients with cat allergy, ImmuLogic has identified three peptides from Fel d I allergen of cat dander which account for 95% of the T cell reactivity to whole allergen in a group of cat sensitive patients. Patients vary in the epitopes their cells respond to. About 12% of a representative group of patients had T cell responsiveness to only one of the epitopes called IPC-2. From animal experiments we hypothesize that administration of this epitope to patients whose T cells respond to it will alter T cell responsiveness in ways that will specifically inhibit synthesis of IgE antibody to the intact allergen. Patients so treated should also have less inflammatory response to the allergen. We will screen cat sensitive patients who have never received cat dander immunotherapy (desensitization) and identify two groups: one sensitive to the one epitope in question and another sensitive to that epitope and one or more of the others. These subjects will be asked to participate in a study employing synthesized IPC-2. We will administer a dose of the peptide intravenously in comparison with control patients who receive saline injection. Before and several times after, the subjects will have measurements or studies of the following variables: a. T cell proliferation during culture with IPC-2. b. Cytokine expression by lymphocytes during culture with IPC-2 and with Fel d I. c. Skin tests with Fel d I measuring both early and late responses. d. Serum IgE and IgG to Fel d I. e. Histamine release from peripheral blood basophils to cat allergen. f. Spontaneous production of histamine releasing factor by cultured lymphocytes. g. Elisa assays for peptide specific antibodies. h. PBMC synthesis of IgE antibody to Fel d I in the presence of IL-4 and steroid. i. Early and late phase response to respiratory challenge with cat allergen.
| Norman, P S (1997) Responses to T cell tolerogenic peptides. Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf A M :40-4 |
| Norman, P S (1996) Clinical experience with treatment of allergies with T cell epitope containing peptides. Adv Exp Med Biol 409:457-61 |
