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Infection and Immunity, September 2005, p. 5358-5366, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5358-5366.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

Dorothy D. Pless, Gordon Ruthel, Emily K. Reinke, Robert G. Ulrich, and Sina Bavari^*

U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702-5011

Received 1 March 2005/ Returned for modification 18 April 2005/ Accepted 1 May 2005

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.

Editor: J. D. Clements

Present address: Instituto de Neurobiología, Universidad National Autónoma de México, Campus UNAM Juriquilla, 76230 Querétaro, Qro., Mexico.