Therapeutic Activity of a Novel Tick Immunosuppressant

描述（由申请方提供）：本提案的总体目标是评价蜱唾液腺产生的新型免疫抑制蛋白的治疗潜力。 肩胛硬蜱，黑腿蜱，通过多种机制规避宿主的免疫反应，因为它获得了它的血液餐。 Salp 15是通过筛选蜱唾液腺cDNA文库鉴定的蛋白。 重组Salp 15在体外抑制CD4+ T细胞的增殖和活化，并且在体内也具有活性。 然而，重组Salp 15的活性低于唾液中发现的天然形式的蛋白质。 在阶段I实验中，将确定天然Salp 15的一级结构。 这些信息将用于合成一种新形式的重组Salp 15，其氨基酸序列与天然蛋白质的氨基酸序列精确匹配。 将在体外和体内测定这种新的重组蛋白的活性。 将纯化毫克量的适用于动物的这种新的重组Salp 15。 该蛋白的活性将在人类疾病即鼠莱姆关节炎的动物模型中进行测试。 在II期实验中，Salp 15的活性将在人类疾病的其他动物模型中进行测试。

DESCRIPTION (provided by applicant): The overall objective of this proposal is to evaluate the therapeutic potential of a novel immunosuppressant protein produced by tick salivary glands. Ixodes scapularis, the black-legged tick, circumvents the host's immune response by multiple mechanisms as it obtains its blood meal. Salp 15 is a protein identified by screening a tick salivary gland cDNA library. Recombinant Salp 15 inhibits the proliferation and activation of CD4+ T cells in vitro, and is also active in vivo. However, recombinant Salp 15 is less active than the native form of the protein found in saliva. In phase I experiments, the primary structure of native Salp 15 will be determined. This information will be used to synthesize a new form of recombinant Salp 15 whose amino acid sequence matches precisely that of the native protein. The activity of this new recombinant protein will be determined in vitro and in vivo. Milligram amounts of this new recombinant Salp 15 suitable for use in animals will be purified. The activity of this protein will be tested in an animal model of human disease, namely murine Lyme arthritis. In Phase II experiments the activity of Salp 15 will be tested in additional animal models of human disease.