PROCESSING OF MYCOBACTERIAL GLYCOPEPTIDOLIPID ANTIGENS

该提案的主要目的是调查 某些分枝杆菌糖脂抗原被宿主巨噬细胞吸收，从而 更好地了解分枝杆菌感染中的吞噬后事件 可以实现。 这一目标将通过使用放射性标记来实现 从胞内分枝杆菌中分离出糖肽脂 (GPL) 抗原 鸟分枝杆菌-M 血清型 20。细胞内-瘰疬 （MAIS）血清复合物。 MAIS 复合体代表一组非结核性 分枝杆菌可导致人类严重肺部感染，其中更多 最近发现是重要的条件致病菌 患有获得性免疫缺陷综合症（艾滋病）的患者。 的 血清型 20 的 GPL 抗原将通过内部放射性标记 标记技术并与免疫细胞化学结合使用 作为探针的程序来确认和监测它们与小鼠的关联 腹膜巨噬细胞。 一旦 GPL 吞噬后关联 抗原已经确定，将启动实验进行研究 GPL 抗原对巨噬细胞功能有何影响。 这些初步的 实验，重点关注 GPL 抗原的可能性 有助于抑制免疫功能，将检查其效果 GPL抗原对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。 由于越来越多的证据表明抗原与 巨噬细胞可以刺激迟发型超敏反应，进而产生 更有效的细胞介导的免疫反应，这一结果 调查可能对东道国产生重要影响 对与艾滋病患者相关的分枝杆菌感染的反应。 如果 GPL抗原可以与巨噬细胞结合，未来的实验 将旨在确定的有效性 巨噬细胞相关抗原引发细胞介导的免疫 回应。 或者，将 GPL 抗原定位于内部或之上 宿主巨噬细胞可能会影响巨噬细胞之间的正常通讯 以及其他免疫学上重要的细胞，例如 B 和/或 T 淋巴细胞。 由于这些细胞相互作用对于正确的免疫学至关重要 对细胞内病原体的反应性，一项研究 涉及 GPL 抗原的吞噬后事件可能很重要 了解艾滋病患者缺乏反应能力 MAIS 血清复合体中的非结核分枝杆菌。

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.