Persistence of zinc-binding bacterial superantigens at the surface of antigen-presenting cells contributes to the extreme potency of these superantigens as T-cell activators.
Bacterial superantigen intoxication causes massive overactivation of T cells, which can result in potentially lethal toxic shock. Superantigens fall into two groups: superantigens such as staphylococcal enterotoxin B (SEB) that contain a single generic binding site for major histocompatibility complex class II (MHC-II) and more potent superantigens such as SEA with a second, zinc-dependent MHC-II binding site that enables them to cross-link adjacent MHC-II molecules. We found that although all superantigens bound rapidly to the surface of human B cells, zinc-binding superantigens largely remained at the cell surface for at least 40 h. In contrast, single-binding-site superantigens were greatly depleted from the surface by 4 h. Subcellular fractionation and confocal microscopy revealed that some SEB entered lysosomal compartments, but SEA remained almost undetectable inside cells at 20 h. SEA and SEB mutants that do not bind MHC-II were trafficked rapidly to lysosomal compartments. Our findings suggest that the persistence of SEA and other zinc-dependent, cross-linking superantigens on the surface of antigen-presenting cells contributes to their potency as T-cell activators.
Pless
Dorothy D
DD
U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Frederick, MD 21702-5011, USA.
Ruthel
Gordon
G
Reinke
Emily K
EK
Ulrich
Robert G
RG
Bavari
Sina
S
D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000382:microbiology; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D018613:Microscopy, Confocal; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D015032:Zinc / Q000378:metabolism*
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D015032:Zinc