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Autoantigen and proteins structurally related thereto for use in immunotherapy of autoimmune diseases

机译:用于自身免疫疾病免疫治疗的自身抗原和与其结构相关的蛋白质

摘要

The present invention relates to novel peptides derived from the autoantigen HC gp-39, said peptides comprising at least one of the amino acid sequences FGRSFTILAS (SEQ ID No. 1), FTLASSETG (SEQ ID No. 2), YDDQESVKS (SEQ ID No. 3) and FSKIASNTQ (SEQ ID No. 4). The peptides resemble MHC Class II restricted T-cell epitopes present on the autoantigen HC gp-39 in articular cartilage. HC gp-39, proteins comprising an amino acid sequence which exhibits at least 50% homology with the amino acid sequence YKLVCYYTSWSQYREGDGSCFPDALDRFLCTHIIYSFANISND (SEQ ID No: 10) and said peptides can be used in antigen-specific treatment of articular cartilage destruction in autoimmune diseases in mammals to induce systemic tolerance of the immune system. The autoantigen HC gp-39, proteins comprising an amino acid sequence which exhibits at least 50% homology with the amino acid sequence YKLVCYYTSWSQYREGDGSCFPDALDRFLCTHIIYSFANISND (SEQ ID NO: 10) and said peptides are also suitable to induce arthritis in animals, preferably mice. The invention furthermore relates to pharmaceutical compositions comprising said autoantigen and/or said peptides, a diagnostic method for the detection of autoreactive T cells in a test sample and test kits to be used in said method.
机译:本发明涉及衍生自自身抗原HC gp-39的新型肽,所述肽包含氨基酸序列FSGRSFTILAS(SEQ ID No.1),FTLASSETG(SEQ ID No.2),YDDQESVKS(SEQ ID No. 3)和FSKIASNTQ(SEQ ID No.4)。该肽类似于关节软骨中自身抗原HC gp-39上存在的MHC II类限制性T细胞表位。 HC gp-39,包含与氨基酸序列YKLVCYYTSWSQYREGDGSCFPDALDRFLCTHIIYSFANISND(SEQ ID No:10)表现出至少50%同源性的氨基酸序列的蛋白质,并且所述肽可用于抗原特异性治疗自体免疫疾病中的关节软骨破坏哺乳动物诱导免疫系统的系统耐受。自身抗原HC gp-39蛋白,包含与氨基酸序列YKLVCYYTSWSQYREGDGSCFPDALDRFLCTHIIYSFANISND(SEQ ID NO:10)表现出至少50%同源性的氨基酸序列,并且所述肽也适用于在动物(优选小鼠)中诱导关节炎。本发明还涉及包含所述自身抗原和/或所述肽的药物组合物,用于检测测试样品中自身反应性T细胞的诊断方法以及在所述方法中使用的测试试剂盒。

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