NEISSERIAL PORINS AND ANTIGEN PRESENTING CELL

奈瑟氏球菌孔蛋白和抗原呈递细胞

• 批准号: 2005498
• 负责人: LEE Mark WETZLER
• 金额: $ 17.4万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2005498
• 关键词: B lymphocyte; Neisseria gonorrhoeae; Neisseria meningitidis; Neisseriaceae; antigen presenting cell; athymic mouse; bacterial polysaccharides; bacterial toxins; cytokine; enzyme linked immunosorbent assay; genetically modified animals; laboratory mouse; pore forming protein; toxin metabolism

DESCRIPTION (Adapted from the applicants abstract): The overall aim of this proposal is to characterize and define the mechanism behind the adjuvant activity of Neisserial porins by extending our work regarding the effect of the porins on antigen presenting cells. The Neisserial porins to be used are protein IA (PIA) and protein IB (PIB) from the gonococcus and class 1 or 3 proteins from the meningococcus (C1 and C3 respectively). Neisserial porins have been investigated as adjuvants in vaccines using pneumococcal polysaccharide, Hemophilus polysaccharide (currently in use), malarial peptides, human gangliosides (as anti-melanoma vaccines), etc. as antigens. Understanding the mechanism behind the Neisserial porins immuno-potentiating ability will aid in the more effective use as adjuvants. Neisserial porins can increase the expression of the ligand B7-2 on B lymphocytes, which is an important mediator of T lymphocyte costimulation, and induce B cells to proliferate and to secrete immunoglobulin nonspecifially. To aid in investigating the mechanism of the porins immuno-potentiating ability and to connect the effect of the porins on antigen presenting cells to their adjuvant activity, this proposal with the following aims is submitted. The first aim will be to bridge the in vitro effect of the porins on B cells, as characterized by increased B7-2 expression, to the porins' adjuvant activity. This will be accomplished by using the porins as adjuvants in immunizations of B7-2 knockout mice, nude mice of CD3 transgenic mice. The second aim will be to discern if the porins can increase specific in vitro antibody towards bacterial capsular polysaccharides, again bridging the finding that porins can activate B cells to the porins's adjuvant activity. In addition, this aim will define the role of cytokines in the porins' adjuvant ability. The third aim will be to continue our studies on the ability of porins to stimulate murine B cells and discern if they affect other murine antigen presenting cells (macrophages/monocytes and dendritic cells) in a similar manner. The final aim will be to investigate whether Neisserial porins have a similar manner. The final aim will be to investigate whether Neisserial porins have a similar effect on human antigen presenting cells. If these aims are accomplished, the understanding of the Neisserial porins' effects on lymphocytes and antigen presenting cells will be greatly enhanced, and the use of the porins and other microbial substances as adjuvants can be improved.

描述（改编自申请人摘要）：此的总体目的 建议是表征和定义佐剂背后的机制 通过扩展我们的工作 抗原呈现细胞上的孔蛋白。 用于使用的奈瑟孔孔 是蛋白IA（PIA）和蛋白IB（PIB），来自淋球菌和1类或 来自脑膜炎球菌的3个蛋白质（分别为C1和C3）。 Neiserial 使用肺炎球菌研究了孔蛋白作为疫苗中的佐剂 多糖，血友病多糖（目前正在使用），疟疾 作为抗原，肽，人为剂（作为抗黑色素瘤疫苗）等。 了解Neisserial Porins Immuno-Potentiating的机制 能力将有助于更有效的用作佐剂。 奈瑟孔孔 可以增加B淋巴细胞上配体B7-2的表达，这是 T淋巴细胞共刺激的重要介质，并诱导B细胞 扩散并分泌免疫球蛋白非重新分泌。 帮助进来 研究孔蛋白免疫态度的机制，并 将孔蛋白对抗原呈递细胞的影响连接到其 辅助活动，提出了以下目的的提案。 这 第一个目的是桥接孔蛋白对B细胞的体外效应，因为 以b7-2表达增加的特征在于波林佐剂 活动。 这将通过在 B7-2敲除小鼠的免疫，CD3转基因小鼠的裸鼠。 这 第二个目的是辨别孔蛋白是否可以在体外增加特定 抗细菌囊囊多糖的抗体，再次桥接 发现孔蛋白可以将B细胞激活到孔蛋白的辅助活性。 此外，该目标将定义细胞因子在波林的作用 辅助能力。 第三个目标是继续我们的研究 孔蛋白刺激鼠B细胞并辨别出影响的能力是否影响 其他鼠抗原呈递细胞（巨噬细胞/单核细胞和树突状 细胞）以类似的方式。 最终目标是调查是否 奈瑟孔孔具有类似的方式。 最终目标是 研究奈瑟氏骨毒素是否对人类抗原有相似的作用 呈现细胞。 如果实现了这些目标，对 Neiserial Porins对淋巴细胞和抗原呈现细胞的影响将 大大增强，并使用孔子和其他微生物 可以改善作为佐剂的物质。