PROCESSING OF MYCOBACTERIAL GLYCOPEPTIDOLIPID ANTIGENS

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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.