MHC CLASS IB IMMUNITY TO AN INTRACELLULAR PATHOGEN

描述(改编自申请人的摘要)：保护性免疫 对单核细胞增多性李斯特菌的反应用于研究细胞免疫 细胞内的细菌。一个必要的毒力决定因素是分泌物。 李斯特菌溶血素O(LLO)。李斯特菌特异性CD8+T细胞具有细胞毒作用 在体外，这些效应物能溶解L.单核细胞增多症的感染靶点。在BALB/c中 已分离出KD限制性的小鼠(H2d)、CD8+CTL，并且a 与LLO的aa91-99相对应的纳米肽由 MHC Ia类分子。也描述了L10特异性的CD8+T细胞 单核细胞增多性乳杆菌在MHC类IB限制性感染靶点中的作用 抗原提呈分子被编码在T区内 多态较少的MHC I类分子家族。目标1中的研究将 确定LLO是否是MHC Class Ib限制性的免疫显性抗原 抗李斯特菌CTL。AIM 2的研究将确定MHC Ib类物质是否 限制性抗李氏杆菌细胞在体内具有保护性。AIM 3中的研究 将确定LLO衍生的MHC Ib类限制性CTL表位。结果 这些研究将提供对MHC Ib类的作用的理解 限制性效应细胞在保护性免疫反应中的作用 细胞内病原体。

DESCRIPTION (Adapted from the applicant's abstract): The protective immune response to L. monocytogenes is used to investigate cell-mediated immunity to intracellular bacteria. A necessary virulence determinant is secretion of listeriolysin O (LLO). Listeria-specific CD8+ T cells are cytotoxic in vitro, these effectors lyse L. monocytogenes infected targets. In BALB/c mice (H2d), CD8+ CTLs have been isolated which are Kd restricted, and a nanomer peptide corresponding to aa91-99 of LLO shown to be presented by the MHC Class Ia molecule. LLO-specific CD8+ T-cells have also been described which lyse L. monocytogenes infected targets in an MHC Class IB restricted manner; the antigen presenting molecule is encoded within the T-region of a less polymorphic family of MHC Class I molecules. Studies in Aim 1 will determine if LLO is an immuno-dominant antigen for MHC Class Ib restricted antilisterial CTLs. Studies in Aim 2 will determine if MHC Class Ib restricted anti-listerial cells are protective in vivo. Studies in Aim 3 will identify the LLO-derived MHC Class Ib-restricted CTL epitope. Results from these studies will provide an understanding of the role of MHC Class Ib restricted effector cell in the protective immune response to an intracellular pathogen.