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REGULATION OF ANTIBODY RESPONSE TO BACTERIAL ANTIGENS

对细菌抗原的抗体反应的调节

基本信息

批准号：
3221413
负责人：
CHRISTOPHER E TAYLOR
金额：
$ 10.45万
依托单位：
ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-01 至 1989-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3221413
关键词：
Haemophilus influenzae Streptococcus mutans antibacterial antibody antibody formation bacterial antigens bacterial polysaccharides clone cells cortisone cyclophosphamide helper T lymphocyte immunoregulation leukocyte activation /transformation radiation sensitivity suppressor T lymphocyte surface antigens

项目摘要

The long term objective of this project is to establish the precise mechanisms by which T-cells regulate the antibody response to bacterial polysaccharide antigens (BPA) and how this information can be used in the prevention of specific diseases (dental caries, peridontal disease, pneumonia, etc.). It is known that aberrent immune responses to BPA play a role in the predisposition to some of these diseases, such as juvenile peridontitis. Three major goals will be accomplished in the proposed studies. First, monoclonal antibodies to T-cell surface and products of the I region of the H-2 complex will be used to better define the complex regulatory role that T-cells play in antibody production. Four monoclonal antibodies (anti-Ia, anti-I-J, and anti-Lym 22 and 21) and an allo-antiserum (anti-Qa 1) will be used to further characterize suppressor (Lyt 2+) and amplifier (Lyt 1+) T-cells which regulate the antibody response to pneumococcal polysaccharide type III (SSS-III). The characterization of the regulatory cells will be done by the depletion of specific subpopulations with antibody and complement and then testing the residual cells for activity. Second, an in vitro system for the induction of antibody response to SSS-III will be established in order to identify the cells involved in the production of factors released from regulatory T-cells. This analysis will be accomplished, first, by using whole spleen cells, then enriched populations and finally T-cell clones. By this in vitro system we will also determine the recognition signals involved in the activation of regulatory T-cells. We have preliminary evidence that regulatory T-cells in this system (SSS-III) recognize idiotypic determinants (ID) on B cells. It is possible that such a recognition of ID in BPA systems replaces the need to recognize self MHC determinants which is known to occur in most non-bacterial antigens. Third, we will determine if the same immunoregulatory mechanisms established for SSS-III can be directly applied to other streptococci, e.g., Streptococcus mutans, the etiologic agent for dental caries, and three other BPA (meningococcal A, C and Haemophilus influenzae) known to be immunogenic in mice.

该项目的长期目标是建立精确的 T细胞调节细菌抗体应答的机制多糖抗原（BPA）以及如何将这些信息用于预防特定疾病（龋齿，牙周病，肺炎等）。众所周知，对BPA的异常免疫反应在在易感性的一些这些疾病，如青少年，牙周炎三大目标将在拟议中实现问题研究第一，单克隆抗体的T细胞表面和产物的I区 H-2复合物将用于更好地定义复合物的调节作用。 T细胞在抗体产生中的作用。四种单克隆抗体（抗Ia、抗I-J和抗Lym 22和21）和同种抗血清（抗Qa 1)将用于进一步表征抑制器（Lyt 2+）和放大器 (Lyt 1+）调节对肺炎球菌抗体应答的T细胞多糖III型（SSS-III）。监管机构的特征细胞将通过特定亚群的消耗来完成，抗体和补体，然后检测残留细胞的活性。第二，用于诱导抗体应答的体外系统， SSS-III将被建立，以确定参与的细胞，从调节性T细胞释放的因子的产生。该分析将首先，通过使用整个脾细胞，然后富集最后是T细胞克隆。通过这个体外系统，我们将还确定涉及激活的识别信号，调节性T细胞。我们有初步证据表明调节性T细胞在该系统中（SSS-III）识别B细胞上独特型决定簇（ID）。 BPA系统中的这种ID识别有可能取代需要识别自身MHC决定因素，这是已知发生在大多数非细菌抗原。第三，我们将确定是否相同的免疫调节机制，建立SSS-III可以直接应用于其他链球菌，例如，在一个实施例中，变形链球菌，龋齿的病原体，和另外三种BPA（脑膜炎球菌A，C和流感嗜血杆菌）已知是免疫原性。