ANTIGEN-SPECIFIC T-CELL RECEPTOR ANTAGONISM BY ANTIGEN-PRESENTING CELLS TREATED WITH THE HEMOLYSIN OF LISTERIA-MONOCYTOGENES - A NOVEL TYPEOF IMMUNE ESCAPE

We have examined the influence of listeriolysin O (LLO), the hemolysin secreted by the pathogenic bacterium Listeria monocytogenes, on major histocompatibility complex class II-dependent T cell activation. Stim ulation of T cells by native antigens but not by peptides is inhibited upon pretreatment of antigen-presenting cells (APC) with LLO. Experim ents presented here reveal that this inhibition is not due to a lack i n processing of antigen by APC but is the result of an irreversible in activation of T cells that recognize antigen on LLO-treated APC. Incub ation of mixtures of two different T cells where only one antigen was presented on LLO-treated APC suggested that T cell inactivation is ant igen specific. The inactivation was dominant and could be observed eve n in the presence of amounts of synthetic peptides that normally lead to T sell responses. This condition is reminiscent of the T cell inhib ition observed when antagonistic and stimulatory peptides are added to APC at the same time. Our results thus reveal a novel type of interfe rence by pathogens with antigen presentation and T cell stimulation th at could give the pathogen a decisive advantage in dissemination and d isease.