Antigen-specific T cell receptor antagonism by antigen-presenting cells treated with the hemolysin of Listeria monocytogenes: a novel type of 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. Stimulation of T cells by native antigens but not by peptides is inhibited upon pretreatment of antigen-presenting cells (APC) with LLO. Experiments presented here reveal that this inhibition is not due to a lack in processing of antigen by APC but is the result of an irreversible inactivation of T cells that recognize antigen on LLO-treated APC. Incubation of mixtures of two different T cells where only one antigen was presented on LLO-treated APC suggested that T cell inactivation is antigen specific. The inactivation was dominant and could be observed even in the presence of amounts of synthetic peptides that normally lead to T cell responses. This condition is reminiscent of the T cell inhibition observed when antagonistic and stimulatory peptides are added to APC at the same time. Our results thus reveal a novel type of interference by pathogens with antigen presentation and T cell stimulation that could give the pathogen a decisive advantage in dissemination and disease.
Darji
A
A
Division of Cell Biology and Immunology, National Research Centre for Biotechnology, Braunschweig, Germany. ada@gbf-braunschweig-de
Stockinger
B
B
Wehland
J
J
Chakraborty
T
T
Weiss
S
S
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000494:pharmacology; D001427:Bacterial Toxins; D002460:Cell Line; D000939:Epitopes / Q000187:drug effects*; D005260:Female; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006460:Hemolysin Proteins / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000187:drug effects; D006825:Hybridomas; D008089:Listeria monocytogenes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D000939:Epitopes; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; C038705:hlyA protein, Listeria monocytogenes