PROCESSING OF MYCOBACTERIAL GLYCOPEPTIDOLIPID ANTIGENS

这项提案的主要目标是调查 宿主巨噬细胞的某些分枝杆菌糖脂抗原 更好地了解分枝杆菌感染的吞噬后事件 是可以实现的。这一目标将通过使用无线电标记 胞内分枝杆菌糖肽脂(GPL)抗原的分离 鸟型分枝杆菌-M。胞内--华支睾吸虫 (MAIS)血清复合体。MAIS复合体代表了一组非结核 可导致人类严重肺部感染的分枝杆菌，以及 最近被发现是重要的条件致病菌 患有获得性免疫缺陷综合征(艾滋病)的患者。这个 血清型20的GPL抗原将通过内标记的方法进行放射性标记 标记技术并与免疫细胞化学结合使用 作为探针的程序，用于确认和监控它们与鼠标的关联 腹膜巨噬细胞。GPL的一次吞噬后结合 抗原已经确定，将开始进行实验研究 GPL抗原对巨噬细胞功能有何影响。这些初步的 实验，这些实验将集中在GPL抗原 有助于抑制免疫功能，将检验其效果 GPL抗原对小鼠淋巴因子产生和淋巴细胞增殖的影响 有丝分裂原刺激淋巴细胞。 因为越来越多的证据表明，抗原与 巨噬细胞可以刺激迟发性超敏反应，进而产生 更有效的细胞介导的免疫反应，其结果是 调查可能会对东道主产生重要影响 对艾滋病患者相关分枝杆菌感染的反应。如果 GPL抗原可以与巨噬细胞相关，未来的实验 将被设计用来确定 巨噬细胞相关抗原在诱导细胞免疫中的作用 回应。或者，GPL抗原在体内或之上的定位 宿主巨噬细胞可能会影响巨噬细胞之间的正常通讯 以及其他免疫上重要的细胞，如B和/或T淋巴细胞。 因为这些细胞间的相互作用在适当的免疫学中是必不可少的 对细胞内病原体的反应性，对 涉及GPL抗原的吞噬后事件可能在 理解艾滋病患者表现出的缺乏反应性 Mais血清复合体中的非结核分支杆菌。

The main objective of this proposal is to investigate the processing of certain mycobacterial glycolipid antigens by host macrophages so that a better understanding of postphagocytic events in mycobacterial infections can be achieved. This objective will be accomplished by using radiolabeled glycopeptidolipid (GPL) antigens isolated from Mycobacterium intracellulare serovar 20 of the Mycobacterium avium-M. intracellulare- M. scrofulaceum (MAIS) serocomplex. The MAIS complex represents a group of nontuberculous mycobacteria which can cause severe lung infections in man and which more recently have been found to be important opportunistic pathogens in patients suffering from Acquired Immune Deficiency Syndrome (AIDS). The GPL antigens of serovar 20 will be radiolabeled by means of internal labeling techniques and used in conjunction with immunocytochemical procedures as probes to confirm and monitor their association with mouse peritoneal macrophages. Once postphagocytic association of the GPL antigens has been established, experiments will be initiated to investigate what effect GPL antigens have on macrophage function. These preliminary experiments, which will focus on the possibility that GPL antigens contribute to suppression of immune functions, will examine the effect of GPL antigens on lymphokine production and lymphocyte proliferation of mitogen stimulated lymphocytes. Because of the increasing evidence that antigens associated with macrophages can stimulate delayed hypersensitivity and in turn generate a more effective cell mediated immune response, the results of this investigation could have important implications with regards to host responses to mycobacterial infections associated with AIDS patients. If the GPL antigens can become associated with macrophages, future experiments will be designed to determine the effectiveness of the macrophage-associated antigens in eliciting cell mediated immune responses. Alternatively, localization of the GPL antigens within or on host macrophages might affect the proper communication between macrophages and other immunologically important cells such as B and/or T lymphocytes. As these cellular interactions are essential in proper immunological responsiveness to intracellular pathogens, an investigation of the postphagocytic events involving the GPL antigens might be important in understanding the lack of responsiveness that AIDS patients demonstrate to nontuberculous mycobacteria in the MAIS serocomplex.