MHC CLASS IB IMMUNITY TO AN INTRACELLULAR PATHOGEN

描述（改编自申请人摘要）：保护性免疫 回应L。单核细胞增多症用于研究细胞介导的免疫 转化为细胞内细菌 一个必要的毒力决定因素是分泌 溶藻素O（LLO）。 李斯特菌特异性CD 8 + T细胞在 在体外，这些效应物裂解L.单核细胞增多症感染的目标。 在BALB/c 小鼠（H2 d），已经分离出Kd限制性的CD 8 + CTL， 对应于LLO的aa 91 -99的纳米聚体肽显示由 MHC Ia类分子。 还描述了LLO特异性CD 8 + T细胞 其裂解L.单核细胞增多症感染的MHC IB类限制性靶点 抗原呈递分子编码在免疫球蛋白的T区内。 较少多态性的MHC I类分子家族。 目标1中的研究将 确定LLO是否是MHC Ib类限制性抗原的免疫显性抗原 抗肿瘤CTL。 目标2中的研究将确定MHC Ib类是否 受限制的抗卵泡细胞在体内具有保护性。 研究目的3 将鉴定LLO衍生的MHC Ib类限制性CTL表位。 结果 从这些研究将提供一个理解的作用，MHC类Ib 限制性效应细胞在保护性免疫反应中的作用 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.