Molecular Mechanisms of Bacterial Superantigen Function
Abstract
Superantigens (SAGS) are a group of immunostimulatory and disease associated proteins of bacterial or viral origin that bind to MHC molecules and certain T cell receptor (TCR) Vb domains and can result in systemic shock and death. Rational design of strategies for prevention or treatments of such diseases may only be possible if we have insights into the mechanisms of T cell activation by SEs. During this grant, we cloned and expressed a human TCR gene in bacculovirus expression system. We demonstrated that the-expressed TCR was properly folded and was functional. We also produced soluble human MHC class II HLA- DR1 and studied the kinetics of its interactions with TCR and different Superantigens by several biochemical and biophysical methods. We measured the kinetics of interactions between SAGs and HLA-DRl and the formation of ternary and guaternary complexes between TCR, DRl, peptides, and SAGs. We discovered that SAGs such as SEA and SEE bind HLA-DRl or HLA-DRl in complex with peptide and enforce rigidity in the groove of MHC II that prevents conformational changes necessary for association with a new peptide, or dissociation of the bound peptide. These observations change the conventional understanding of SAGs/MHC by TCR and helps in clever designs of therapeutics.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA425535
Entities
People
- Scheherazade Sadegh-nasseri
Organizations
- Johns Hopkins University