Superantigen binding to MHC class II molecules is a prerequisite for T cell stimulation. While the presentation of superantigens is not MHC restricted, allelic and isotypic variations in the ability of class II molecules to interact and present these superantigens exist. SEs bind to MHC class II molecules outside of the peptide binding groove, differences in binding affinities of the toxins for class II alleles and isotypes have been shown. In addition, a direct interaction between T cell receptor and MHC class II molecules could be responsible for these differences. In this review we provide a molecular analysis of the interactions of SEs with class II molecules.
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