REGULATION OF ANTIBODY RESPONSE TO BACTERIAL ANTIGENS

该项目的长期目标是建立准确的 T细胞调节细菌抗体应答的机制 多糖类抗原(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)。已知对双酚A的异常免疫反应起到了 在其中一些疾病的易感性中发挥作用，如青少年 牙周炎。计划中将实现三个主要目标 学习。 第一，针对T细胞表面和I区产物的单抗 将被用来更好地定义复杂的监管 T细胞在抗体产生中的作用。四株单抗 (抗Ia、抗I-J和抗Lym 22和21)和异体抗血清(抗Qa 1)将用于进一步表征抑制器(Lyt2+)和放大器 调节肺炎球菌抗体应答的(lyt 1+)T细胞 多糖III型(SSS-III)。规章制度的特征 细胞将通过耗尽特定的亚群来完成 抗体和补体，然后检测残留细胞的活性。 第二，一种诱导抗体应答的体外系统 将建立SSS-III，以确定参与 调节性T细胞释放的因子的产生。这一分析将 首先，通过使用整个脾细胞，然后进行浓缩 种群，最后是T细胞克隆。通过这个体外系统，我们将 还确定在激活过程中涉及的识别信号 调节性T细胞。我们有初步证据表明调节性T细胞 在这个系统中(SSS-III)识别B细胞上的独特型决定因素(ID)。 在BPA系统中，这样的ID识别有可能取代 需要识别已知在大多数情况下发生的自身MHC决定因素 非细菌抗原。 第三，我们将确定相同的免疫调节机制是否 为SSS-III建立的可直接应用于其他链球菌， 例如，引起龋齿的致病菌变形链球菌，以及 已知的另外三种双酚A(脑膜炎双球菌A、C和流感嗜血杆菌)是 在小鼠体内具有免疫原性。

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.