Neisserial Porins and Antigen Presenting Cells

奈瑟氏球菌孔蛋白和抗原呈递细胞

• 批准号: 7486227
• 负责人: LEE Mark WETZLER
• 金额: $ 43.93万
• 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 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7486227
• 关键词: Adjuvant; Amino Acids; Antigen Presentation; Antigen-Presenting Cells; B-Lymphocytes; Bacterial Outer Membrane Proteins; Binding; Binding Sites; Biological Assay; Cells; Class; Data; Dendritic Cells; Drosophila genus; Extracellular Domain; Family; Goals; Immune; Immune response; Immunologic Adjuvants; Japan; Knowledge; Ligands; Lipoproteins; MHC Class II Genes; Mediating; Mediator of activation protein; Membrane; Mycoplasma; Natural Immunity; Neisseria gonorrhoeae protein I; Numbers; Organism; Pattern; Pattern recognition receptor; Peptidoglycan; PorB porin; Process; Production; Proteins; Role; Signal Transduction; Staphylococcus aureus; Structure; TLR1 gene; TLR2 gene; TLR6 gene; Toll-Like Receptor 1; Toll-like receptors; Work; adapter protein; cytokine; immunogenic; macrophage; macrophage stimulatory lipopeptide 2; microbial; porin; receptor

DESCRIPTION (provided by applicant): Neisserial porins (gonococcal Protein I [PIA or PIB] or meningococcal class 1 [PorA], 2 or 3 [PorB] proteins) are the major protein constituent of the Neisserial outer membrane. They have significant homology in structure and function amongst themselves and other Gram-negative porins. These porins have been shown to be potent immune adjuvants and we have demonstrated that this related to their ability to activate antigen presenting cells (APC), and upregulate the expression of the costimulatory molecule CD86 and class II MHC. During the last cycle of this proposal, we have shown that this effect of porins, specifically PorB, on APC is mediated by recognition of PorB by the pattern recognition receptor TLR2 and is MyD88 and TIRAP dependent. The goals of this current proposal are three-fold, 1) Demonstrate the direct interaction of porin PorB with TLR2, 2) determine which TLR2 co-receptor, TLR1 or TLR6 is involved in PorB induced TLR2 mediated activity and 3) determine which APC are essential for porin adjuvant activity and the relationship of this activity to APC antigen presentation and TLR2 activation. The fulfillment of these aims will greatly enhance our knowledge regarding bacterial component interaction with TLRs and the role of TLRs and APC in immune responses.

描述（由申请人提供）：奈瑟氏菌（淋球菌蛋白I [PIA或PIB]或脑膜炎球菌1 [Pora]，2或3 [Porb]蛋白）是奈瑟氏菌外膜的主要蛋白质。它们在彼此之间以及其他革兰氏阴性波的结构和功能方面具有重要的同源性。这些孔蛋白已被证明是有效的免疫佐剂，我们证明这与它们激活抗原呈递细胞（APC）的能力有关，并上调了共刺激分子CD86和II类MHC的表达。在该提案的最后一个循环中，我们表明，PORIN（特别是PORB）对APC的这种影响是通过模式识别受体TLR2识别PORB的介导的，并且是MyD88和TIRAP依赖性的。该目前的提议的目标是三倍，1）证明了孔蛋白PORB与TLR2的直接相互作用，2）确定哪种TLR2共核能，TLR1或TLR6参与PORB诱导的TLR2介导的活性，而3）确定哪个APC对Porin辅助活动和APC Antigen Antigen 2 Activation and Tlr2激活和TLR2激活和TLR2的关系是必不可少的。这些目标的实现将大大增强我们对细菌成分与TLR的相互作用以及TLR和APC在免疫反应中的作用的知识。