NEISSERIAL PORINS AND ANTIGEN PRESENTING CELL

描述（改编自申请人摘要）：本申请的总体目标 建议是表征和定义佐剂背后的机制 活动的奈瑟菌孔蛋白通过扩展我们的工作， 抗原呈递细胞上的孔蛋白。 待用奈瑟球菌孔蛋白 是来自淋球菌的蛋白IA（PIA）和蛋白IB（PIB）和1类或 3种脑膜炎球菌蛋白（分别为C1和C3）。 奈萨里亚 已经研究了孔蛋白作为疫苗中的佐剂， 多糖，嗜血杆菌多糖（目前正在使用），疟疾 肽、人神经节苷脂（作为抗黑素瘤疫苗）等作为抗原。 了解奈瑟氏菌孔蛋白免疫增强的机制 这种能力将有助于更有效地用作佐剂。 奈瑟球菌孔蛋白 能增加B淋巴细胞上配体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 增殖和非特异性分泌免疫球蛋白。 以帮助 研究孔蛋白免疫增强能力的机制， 将孔蛋白对抗原呈递细胞的作用与它们的 辅助活动，本提案的目的如下。 的 第一个目标是桥接孔蛋白对B细胞的体外作用， 其特征在于B7-2表达增加， 活动 这将通过使用孔蛋白作为佐剂来实现， 免疫B7-2基因敲除小鼠、CD 3转基因小鼠的裸鼠。 的 第二个目标是辨别孔蛋白是否可以在体外增加特异性 针对细菌荚膜多糖的抗体，再次桥接 发现孔蛋白可以激活B细胞以发挥孔蛋白的佐剂活性。 此外，这一目标将确定细胞因子在孔蛋白的作用， 辅助能力 第三个目标是继续研究 孔蛋白刺激鼠B细胞并辨别它们是否影响 其它鼠抗原呈递细胞（巨噬细胞/单核细胞和树突状细胞 细胞）以类似的方式。 最终目的是调查是否 奈瑟菌孔蛋白也有类似的方式。 最终目标是 研究奈瑟氏菌孔蛋白是否对人类抗原具有类似作用 呈递细胞 如果这些目标得以实现， 奈瑟菌孔蛋白对淋巴细胞和抗原呈递细胞的作用将 大大提高，并使用孔蛋白和其他微生物 可以改进作为佐剂的物质。

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.