MHC CLASS IB IMMUNITY TO AN INTRACELLULAR PATHOGEN

MHC IB 类对细胞内病原体的免疫力

基本信息

批准号：
2887360
负责人：
H. G. Archie Bouwer
金额：
$ 17.48万
依托单位：
PROVIDENCE PORTLAND MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-07-01 至 2001-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2887360
关键词：
Listeria MHC class I antigen antibacterial agents antigen presentation bacterial antigens bacterial proteins bactericidal immunity cell line cellular immunity cytotoxic T lymphocyte laboratory mouse mutant passive immunization peptide chemical synthesis protein sequence tissue /cell culture virulence

项目摘要

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.

描述（改编自申请人的摘要）：保护性免疫对单核细胞增生乳杆菌的反应用于研究细胞介导的免疫到细胞内细菌。必要的毒力决定因素是分泌物 listeriolysin o（llo）。李斯特菌特异性CD8+ T细胞在细胞毒性中在这些效应子裂解了单核细胞增生的感染靶标。在BALB/c中已经隔离了小鼠（H2D），CD8+ CTL，这些是限制KD的，A 纳米肽对应于与LLO的AA91-99相对应的纳米肽 MHC类IA分子。也已经描述了LLO特异性CD8+ T细胞在MHC类Ib中，lyse L.单核细胞增生剂感染了靶标方式;抗原呈递分子在A的T区域内编码 MHC I类分子的多态性家族较少。 AIM 1的研究将确定LLO是否是限制MHC类IB的免疫主导抗原抗科学CTL。 AIM 2的研究将确定MHC类IB是否受限的抗层细胞在体内具有保护性。 AIM 3的研究将确定LLO衍生的MHC类IB限制的CTL表位。结果从这些研究中将了解MHC类IB的作用保护性免疫反应中的限制性效应细胞细胞内病原体。