NEISSERIAL PORINS AND ANTIGEN PRESENTING CELL

描述(改编自申请者摘要)：本报告的总体目标 建议是表征和定义佐剂背后的机制 通过扩展我们关于NisSerial Pporins的作用的工作 抗原提呈细胞上的孔蛋白。将使用的NeisSerial Pporins 是来自淋球菌的蛋白IA(PIA)和蛋白IB(PIB)，以及1类或 脑膜炎球菌分离蛋白3种(分别为C1和C3)。NeisSerial 孔蛋白作为佐剂已被研究在使用肺炎球菌的疫苗中。 疟疾嗜血杆菌多糖(目前使用) 多肽、人神经节苷脂(作为抗黑色素瘤疫苗)等作为抗原。 了解NeisSerial孔蛋白免疫增强的机制 能力将有助于更有效地使用佐剂。新型连环磷脂酶 可以增加B淋巴细胞表面配体B7-2的表达，这是一种 T淋巴细胞共刺激的重要介质，并诱导B细胞 增殖并非特异性地分泌免疫球蛋白。帮助…… 探讨孔蛋白免疫增强作用的机制及作用机制 将孔蛋白对抗原提呈细胞的影响与它们的 为了加强佐剂活动，现提交本提案，目的如下。这个 第一个目标将是在体外连接孔蛋白对B细胞的影响，因为 以B7-2表达增加为特征的孔蛋白佐剂 活动。这将通过使用孔蛋白作为佐剂在 免疫B7-2基因敲除小鼠、CD3转基因裸鼠。这个 第二个目标将是辨别孔蛋白是否能在体外增加特异性 针对细菌荚膜多糖的抗体，再次架起了 研究发现，孔蛋白可以激活B细胞，发挥孔蛋白的佐剂活性。 此外，这一目标将定义细胞因子在猪的 佐剂能力。第三个目标是继续研究 孔蛋白刺激小鼠B细胞的能力和识别它们是否影响 其他小鼠抗原提呈细胞(巨噬细胞/单核细胞和树突状细胞 细胞)以类似的方式。最终目标将是调查是否 NeisSerial Porins也有类似的方式。最终目标将是 研究新序列孢子蛋白是否对人类抗原有类似的影响 呈现细胞。如果实现了这些目标，对 奈瑟菌素对淋巴细胞和抗原提呈细胞的影响 得到极大的提高，并利用孔蛋白和其他微生物 作为佐剂的物质可以改进。

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.