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ANTI-IDIOTYPE REGULATION OF TIMOTHY IGE FORMATION

Timothy IGE 形成的抗独特型调控

基本信息

批准号：
3128866
负责人：
ARTHUR MALLEY
金额：
$ 9.38万
依托单位：
OREGON REGIONAL PRIMATE RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-03-01 至 1986-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3128866
关键词：
B lymphocyte T lymphocyte antiantibody antiidiotype antibody helper T lymphocyte human tissue immunoglobulin E immunoregulation macrophage monoclonal antibody suppressor T lymphocyte surface antigens tissue /cell culture

项目摘要

The objective of this proposal is to study the in vitro induction of antigen-specific suppressor T cells by anti-idiotypic antibodies and soluble antigen-specific suppressor factors. Preliminary studies indicate that anti-idiotypic antibody (anti-Id) and affinity-purified timothy grass pollen AgB-specific suppressor factor (TSF) and anti-idiotype factor (anti-Id factor) induce significant levels of suppressor T (TS) cells in vitro. The proposed experiments will attempt to 1) derive the optimal culture conditions for the induction of TS cells, 2) determine the nature of the TS cells induced (TS1 and TS2), 3) determine the role of Fc+ cells in "presentation" of anti-Id, TSF, and anti-Idfactor to T cells, and 4) determine the cell surface antigen characteristics of the cell induced by anti-Id-bound Fc+ cells. Important new information regarding the constant region of TSF and anti-Id factor would be obtained from studies indicating that Fc+ cells play a role in the induction of TS cells by these factors secreted from TS1 and TS2 cells. The amounts of IgG or IgE antibody formed and the levels of TSF and anti-Id factor extracted from enriched TS1 and TS2 cell populations will be determined by ELISA methods. The availabiltiy of monoclonal anti-T-helper factor (anti-THF) antibody will permit us to determine if the idiotypic determinants expressed on T-helper, T-suppressor, and B cells are identical or only appear identical due to the heterogeneity of our rabbit anti-THF and anti-IgEid (anti-Id) antibodies. One of our long-term goals is to develop materials that will suppress IgE responses of timothy-sensitive patients. We have proposed trying to develop antigen-specific human TS cells by using 1) affinity-purified human timothy IgE to prepare anti-idiotypic antibodies, 2) photooxidized timothy AgB in cultures with macrophage-depleted peripheral blood lymphocytes, and 3) anti-idiotypic antibody made against murine T and B cell products that react to the identical antigenic determinant as humans allergic to timothy pollen. These studies will involve the in vitro cultures of peripheral blood lymphocytes in mini-Marbrook chambers. The harvested cells will be analyzed for their ability to suppress timothy-specific IgE formation in vitro.

本建议的目的是研究体外诱导成纤维细胞的能力。抗独特型抗体诱导的抗原特异性抑制T细胞可溶性抗原特异性抑制因子。初步研究表明抗独特型抗体(抗ID)和亲和纯化的蒂莫西·格拉斯花粉银杏特异性抑制因子和抗独特型因子 (抗ID因子)诱导小鼠T(TS)抑制细胞水平显著升高体外培养。拟议的实验将尝试1)得出最优的诱导TS细胞的培养条件，2)决定细胞的性质在诱导的TS细胞(TS1和TS2)中，3)确定Fc+细胞的作用将抗-ID、TSF和抗-ID因子“呈现”给T细胞，以及4) 细胞表面抗原特性的测定抗ID结合的Fc+细胞。关于常量的重要新信息 TSF的区域和抗ID因子将从研究中获得 Fc+细胞在这些因子诱导TS细胞中的作用由TS1和TS2细胞分泌。免疫球蛋白抗体或免疫球蛋白E抗体的生成量从浓缩的TS1和TS1中提取的TSF和抗ID因子水平 TS2细胞的数量将通过ELISA法进行测定。可用性抗T辅助因子(抗THF)的单抗将使我们能够确定T辅助细胞上表达的独特型决定因素， T-抑制子和B细胞是相同的或只是看起来相同，因为我们的兔抗THF和抗IgEid(抗ID)抗体的异质性。我们的长期目标之一是开发抑制IgE的材料蒂莫西敏感患者的反应。我们已经提议尝试用亲和纯化的人TS细胞制备抗原特异性的人TS细胞 Timothy IgE制备抗独特型抗体，2)光氧化Timothy 巨噬细胞耗尽的外周血淋巴细胞培养中的AGB，以及 3)针对小鼠T和B细胞产物制作的抗独特型抗体对相同的抗原决定簇的反应就像人类对蒂莫西过敏一样花粉。这些研究将涉及外周血细胞的体外培养。迷你马布鲁克小室里的血淋巴细胞。收获的细胞将是分析它们抑制Timothy特异性IgE形成的能力体外培养。