Staphylococcal enterotoxin H - structure and function of a superantigen

Abstract: The aim of this thesis was to characterise the biological functions of the superantigen staphylococcal enterotoxin H (SEH). Superantigens are highly immunostimulatory proteins, which crosslink T cells and antigen presenting cells (APCs). SEH is included in a family of staphylococcal enterotoxins (SEs) produced by certain strains of Staphylococcus aureus. The three-dimensional fold of SEH was determined and showed a high overall similarity with related superantigens, but some differences in the regions traditionally involved in T cell receptor (TCR) binding were observed. Superantigens bind to major histocompatibility complex (MHC) class II on APCs and SEH revealed the highest affinity ever measured for an SE for MHC class II. SEH bound to the MHC class II beta-chain dependent on Zn2+ and the antigen peptide presented by MHC class II and related Zn2+ coordinating superantigens most likely interact with MHC class II in a similar way. So far, all bacterial superantigens have been suggested to interact with and stimulate T cells in a TCR Vbeta specific manner. However, SEH stimulates T cells very differently as compared to related SEs since it activates human T cells without inducing a TCR Vbeta specific expansion. Moreover, SEH revealed more restricted species specificity than other SEs by not activating rodent T cells and this may be due to the different mode of T cell activation suggested for SEH. In conclusion, SEH reveals interesting features regarding T cell activation and these findings illustrate a much greater biological complexity within the SE family than previously thought.