Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen

Abstract

The structure of a bacterial superantigen, Staphylococcus aureus enterotoxin B, bound to a human class II histocompatibility complex molecule (HLA-DR1) has been determined by X-ray crystallography. The superantigen binds as an intact protein outside the conventional peptide antigen-binding site of the class II major histocompatibility complex (MHC) molecule. No large conformational changes occur upon complex formation in either the DR1 or the enterotoxin B molecules. The structure of the complex helps explain how different class II molecules and superantigens associate and suggests a model for ternary complex formation with the T-cell antigen receptor (TCR), in which unconventional TCR-MHC contacts are possible.

Engineering protein for X‐ray crystallography: The murine major histocompatibility complex class II molecule I‐Ad

“…To date, three different structures of class I1 MHC molecules have been reported for HLA-DRl (Brown et al, 1993;Jardetzky et al, 1994;Stem et al, 1994), HLA-DR3 (Ghosh et al, 1995), and I-Edk (Fremont et al, 1996). In these human and mouse class I1 structures, the amino terminal a , and PI domains form the characteristic peptide binding groove that was initially described for human (Bjorkman et al, 1987) and mouse (Fremont et al, 1992) MHC class I molecules.…”

“…In general, class I1 MHC molecules will bind peptides that have certain residues located within a nine residue ''core" motif. Peptides bound to a class I1 MHC molecule assume a remarkably regular secondary structure conformation that is similar to a polyproline type 11 ribbon-like helix (Stem et al, 1994;Fremont et a!., 1996;Jardetzky et al, 1996;reviewed in Stem and Wiley. 1994;Wilson, 1996).…”

“…1994;Wilson, 1996). Importantly, a number of conserved side chains, primarily from the two a-helices, interact with main-chain atoms of the bound peptide and help orient and fix the peptide in the groove (Stem & Wiley, 1994;Jardetzky et al, 1996), imparting a degree of sequence-independent peptide binding capability to the MHC molecule.…”

The Staphylococcal Enterotoxins

“…2. In contrast to conventional antigens, intact superantigenic proteins bind to MHC II at a site distinct from the peptide-binding site (Jardetzky et al, 1994). Likewise, the binding site for SAg on the TCR is different from the region involved in recognition and binding of the MHC-peptide complex (Seth etal., 1994).…”

The potential role of superantigens in inflammatory bowel disease

“…Unlike conventional antigens, superantigens are not processed by antigen-presenting cells; indeed proteolysis inhibits their superantigen activity [16,17]. Recent crystallographic data confirm that superantigens bind outside the pep tide-binding groove [18]. The exact location differs for each superantigen, so that SEB binds to the Q1 domain of DRI, whereas mutational studies suggest that SEA binds to the /31 domain, and TSST-1 binds to both a\ and /?1 domains [19,20].…”