BACTERIAL SUPERANTIGEN PROCESSING AND PRESENTATION

Abstract

Bacterial superantigens (BSAgs) are a unique class of antigens capable of cross-linking major histocompatibility complex (MHC) class II molecules to particular T-cell antigen receptor variable segment (TCR Vβ) causing various pathogenic syndromes. Unlike classical protein antigens, BSAgs bypass the specificity of interaction of MHC and TCR. Exagerated T cell proliferation followed by a state of T cell non-responsiveness (anergy) are the characteristic features of BSAgs. T lymphocytes obtained from mice injected with low microgram amounts of BSAg were unresponsive to successive BSAg challenge. A possible mechanism of this anergic response was investigated by studying the kinetic interactions of BSAgs with MHC class II molecules, that formed saturated complexes within three minutes. These cell surface complexes remained on the cell surface for an extended length of time and were biologically active. Interestingly, SEA had the highest amount of binding and one of the slowest dissociation rates. The stability of these complexes was tested in endosomal/lysosomal hydrogen ion concentrations similar to the pH where conventional antigen peptides dislocate from class II molecules. Remarkably, complexes of BSAg and MHC class II molecules were stable even at lysosomal pH. To further examine BSAgs' processing and presentation, subcellular organelles were fractionated using Percoll density-gradients. The subcellular distribution of SEA and SEB was comparable with the majority of each found on the plasma membrane, although more SEB could be detected in the lysosomes. Conventional antigen reached far into the acidic endocytic vesicles after a short incubation period. Furthermore, distribution of the conventional antigen was altogether different as it was observed throughout subcellular compartments, but not on the plasma membrane. These results indicate that BSAgs are internalized and processed in a way that may differ from conventional antigens. Thus, constitutive transports of BSAgs from the plasma membrane to MHC class II peptide-loading compartment, through endosomes and lysosomes, occur at a much reduced rate and this phenomenon may have far reaching consequences on how T cells react to these unusual antigens.