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Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen
T S Jardetzky1, J H Brown, J C Gorga
1Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Nature
|April 21, 1994
Summary
The structure of Staphylococcus aureus enterotoxin B bound to HLA-DR1 reveals the superantigen binds outside the normal peptide site. This finding explains how superantigens interact with MHC class II molecules and T-cell receptors.
Area of Science:
- Structural Biology
- Immunology
- Microbiology
Background:
- Bacterial superantigens, like Staphylococcus aureus enterotoxin B (SEB), are potent immune activators.
- Major histocompatibility complex (MHC) class II molecules present antigens to T cells.
- Understanding superantigen-MHC interactions is crucial for dissecting immune responses.
Purpose of the Study:
- To determine the high-resolution structure of SEB bound to a human MHC class II molecule, HLA-DR1.
- To elucidate the molecular basis of superantigen engagement with MHC class II.
- To provide insights into the formation of ternary complexes with T-cell receptors (TCRs).
Main Methods:
- X-ray crystallography was employed to determine the complex structure.
- Analysis of protein-protein interactions between SEB and HLA-DR1.
Main Results:
- The structure reveals SEB binds as an intact protein to HLA-DR1.
- Binding occurs outside the conventional peptide-binding groove of HLA-DR1.
- No significant conformational changes were observed in either molecule upon complex formation.
Conclusions:
- The determined structure explains the association mechanism between superantigens and MHC class II molecules.
- It suggests a model for ternary complex formation involving TCRs, highlighting potential unconventional TCR-MHC contacts.
- This structural information aids in understanding superantigen-mediated T-cell activation.