TY - JOUR
T1 - Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II
AU - Li, Yili
AU - Li, Hongmin
AU - Dimasi, Nazzareno
AU - McCormick, John K.
AU - Martin, Roland
AU - Schuck, Peter
AU - Schlievert, Patrick M.
AU - Mariuzza, Roy A.
N1 - Funding Information:
This research was supported by National Institutes of Health (NIH) grants AI36900 and AI42937 and National Multiple Sclerosis Society grant RG2747 (R. A. M.) and NIH grant 36611 (P. M. S.). We thank E. J. Sundberg (Center for Advanced Research in Biotechnology) and K. Karjalainen (Basel Institute for Immunology) for critical reading of the manuscript and D. H. Margulies, J. A. Berzofsky, and R. N. Germain (NIH) for discussions. We also thank L. J. Stern (Massachusetts Institute of Technology) for the gift of HLA-DR1 expression plasmids.
PY - 2001
Y1 - 2001
N2 - MHC class II molecules possess two binding sites for bacterial superantigens (SAGs): a low-affinity site on the α chain and a high-affinity, zinc-dependent site on the β 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 β 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.
AB - MHC class II molecules possess two binding sites for bacterial superantigens (SAGs): a low-affinity site on the α chain and a high-affinity, zinc-dependent site on the β 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 β 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.
UR - https://www.scopus.com/pages/publications/0035129453
UR - https://www.scopus.com/pages/publications/0035129453#tab=citedBy
U2 - 10.1016/S1074-7613(01)00092-9
DO - 10.1016/S1074-7613(01)00092-9
M3 - Article
C2 - 11163233
AN - SCOPUS:0035129453
SN - 1074-7613
VL - 14
SP - 93
EP - 104
JO - Immunity
JF - Immunity
IS - 1
ER -