Related Experiment Videos
Staphylococcal toxins bind to different sites on HLA-DR
M M Chintagumpala1, J A Mollick, R R Rich
1Howard Hughes Medical Institute Laboratory, Baylor College of Medicine, Houston, TX 77030-3498.
Journal of Immunology (Baltimore, Md. : 1950)
|December 1, 1991
Summary
Staphylococcal toxins bind to different sites on HLA-DR molecules, influencing T cell responses. These binding differences, not just affinity, affect how T cells recognize toxin-MHC complexes.
Area of Science:
- Immunology
- Molecular Biology
- Toxinology
Background:
- Staphylococcal enterotoxins (SE) and toxic shock syndrome toxin 1 (TSST-1) are superantigens that bind to MHC class II molecules.
- This binding induces T cell proliferation, mediated by specific T cell receptor (TCR) V beta sequences.
Purpose of the Study:
- To investigate if varying binding affinities of SE and TSST-1 to HLA-DR1 reflect differences in binding site engagement.
- To determine if SEB and TSST-1 bind to distinct or overlapping sites on HLA-DR.
Main Methods:
- Competitive binding assays were employed to study toxin interactions with HLA-DR1.
- Binding affinities of various staphylococcal enterotoxins (SEA, SED, SEE, SEB) and TSST-1 to HLA-DR were assessed.
Main Results:
- SEB and TSST-1 bind to distinct sites on HLA-DR, separate from each other.
- SEA, SED, and SEE appear to bind to the same site(s) as SEB and TSST-1, suggesting at least three distinct binding sites for these toxins on HLA-DR.
- Despite structural similarities, SED and SEE exhibited lower binding affinities to HLA-DR than SEA.
- T cell responses to SED correlated with its lower binding affinity, while SEE elicited strong responses despite low affinity, indicating TCR recognition is also crucial.
Conclusions:
- HLA-DR molecules possess multiple, potentially overlapping, binding sites for staphylococcal toxins.
- Both toxin-MHC class II binding affinity and TCR recognition of the complex influence T cell proliferative responses.