Therapeutic Activity of a Novel Tick Immunosuppressant

描述（由申请人提供）：本申请的总体目标是评估蜱唾液腺产生的一种新型免疫抑制蛋白的治疗潜力。肩胛骨蜱是一种黑腿蜱，它在获取血液时通过多种机制规避宿主的免疫反应。Salp 15是一种通过筛选蜱唾液腺cDNA文库而鉴定的蛋白。重组Salp 15在体外抑制CD4+ T细胞的增殖和活化，在体内也有活性。然而，重组Salp 15比在唾液中发现的天然形式的蛋白质活性低。在第一阶段的实验中，将确定本地Salp 15的主要结构。这些信息将用于合成一种新的重组Salp 15，其氨基酸序列与天然蛋白质完全匹配。该重组蛋白的活性将在体内和体外进行测定。毫克量的这种新的重组Salp 15适用于动物将被纯化。这种蛋白的活性将在人类疾病的动物模型中进行测试，即小鼠莱姆病。在二期实验中，Salp 15的活性将在其他人类疾病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.