CYTOTOXIC T LYMPHOCYTE RESPONSE TO BACTERIAL INFECTION

许多致病细菌入侵并在细胞内繁殖。T淋巴细胞 对于这些细胞内的有效免疫反应是至关重要的 病原体。被感染的细胞处理并向T细胞递送细菌抗原 淋巴细胞使用有趣且不完全的机制 明白了。一种优秀的细胞免疫和细菌抗原模型 加工是小鼠对单核细胞增多性李斯特菌的免疫反应。CD8 细胞毒性T淋巴细胞(CTL)是L。 单核细胞增多性感染与MHC呈递的细菌肽识别 受感染细胞表面的L分子。多肽 最近鉴定了三个CTL克隆的特异性。立法会条例草案91-99 来源于分泌的毒力因子李斯特菌素和P6O217-225 来自分泌的P6O蛋白。这两个都是由H- 2Kd的MHC类L分子。第三个表位为Fr38，是一种分泌型细菌 由H-2M3非经典MHC类L呈递给CTL的多肽 分子。初步研究表明，这三种表位均存在于L. 单核细胞增多症感染细胞的时间不同，感染时间明显不同 数量，因此它们对保护性免疫的相对贡献 回应可能会有所不同。拟议的研究将调查处理过程 以及三个单核细胞增多性乳杆菌CTL表位的呈现。其效果 细胞感染对MHC类L抗原的处理和提呈 将会被确定。它们之间的差异有可能 将探索与保护性免疫相关的CTL表位。 这些研究将加强我们对CTL反应的了解 细胞内的病原体，并可能提出新的保护策略 细胞内的病原体。此外，这些研究将增加我们的 对病原生物与其相互作用的理解 哺乳动物的宿主。

Many pathogenic bacteria invade and multiply within cells. T lymphocytes are critical for an effective immune response to these intracellular pathogens. Infected cells process and present bacterial antigens to T lymphocytes using mechanisms that are interesting and incompletely understood. An excellent model of cellular immunity and bacterial antigen processing is the murine immune response to Listeria monocytogenes. CD8+ cytotoxic T lymphocytes (CTL) are important effectors of immunity to L. monocytogenes infection and recognize bacterial peptides presented by MHC class l molecules on the surface of infected cells. The peptide specificity of three CTL clones has recently been identified. LLO 91-99 derives from the secreted virulence factor listeriolysin and P6O 217-225 comes from the secreted P6O protein. Both are presented to CTL by the H- 2Kd MHC class l molecule. The third epitope, Fr38, is a secreted bacterial peptide that is presented to CTL by the H-2M3 non-classical MHC class l molecule. Preliminary studies show that these three epitopes appear in L. monocytogenes infected cells at different times and in markedly different quantities, and thus their relative contributions to the protective immune response may differ. The proposed studies will investigate the processing and presentation of the three L. monocytogenes CTL epitopes. The effect of cellular infection on MHC class l antigen processing and presentation will be determined. The possibility that the differences between these CTL epitopes may be of relevance to protective immunity will be explored. These studies will enhance our understanding of the CTL response to intracellular pathogens and may suggest new strategies for protection from intracellular pathogens. Additionally, these studies will increase our understanding of the interactions of pathogenic organisms with their mammalian hosts.