Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II.
MHC class II molecules possess two binding sites for bacterial superantigens (SAGs): a low-affinity site on the alpha chain and a high-affinity, zinc-dependent site on the beta chain. Only the former has been defined crystallographically. We report the structure of streptococcal pyrogenic exotoxin C (SPE-C) complexed with HLA-DR2a (DRA*0101, DRB5*0101) bearing a self-peptide from myelin basic protein (MBP). SPE-C binds the beta chain through a zinc bridge that links the SAG and class II molecules. Surprisingly, SPE-C also makes extensive contacts with the MBP peptide, such that peptide accounts for one third of the surface area of the MHC molecule buried in the complex, similar to TCR-peptide/MHC complexes. Thus, SPE-C may optimize T cell responses by mimicking the peptide dependence of conventional antigen presentation and recognition.
Li
Y
Y
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, MD 20850, USA.
Li
H
H
Dimasi
N
N
McCormick
J K
JK
Martin
R
R
Schuck
P
P
Schlievert
P M
PM
Mariuzza
R A
RA
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005098:Exotoxins / Q000737:chemistry* / Q000276:immunology; D015802:HLA-DR2 Antigen / Q000737:chemistry* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008958:Models, Molecular; D004676:Myelin Basic Protein / Q000737:chemistry; D017433:Protein Structure, Secondary; D018089:Superantigens / Q000737:chemistry* / Q000276:immunology; D015032:Zinc / Q000276:immunology*
D001426:Bacterial Proteins; D005098:Exotoxins; D015802:HLA-DR2 Antigen; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D008565:Membrane Proteins; D004676:Myelin Basic Protein; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; C027951:erythrogenic toxin; D015032:Zinc