Journal article
A Mutational Analysis of the Binding of Staphylococcal Enterotoxins B and C3 to the T Cell Receptor β Chain and Major Histocompatibility Complex Class II
The Journal of experimental medicine, Vol.187(6), pp.823-833
03/16/1998
DOI: 10.1084/jem.187.6.823
PMCID: PMC2212189
PMID: 9500785
Abstract
The three-dimensional structure of the complex between a T cell receptor (TCR) β chain (mouse Vβ8.2Jβ2.1Cβ1) and the superantigen (SAG) staphylococcal enterotoxin C3 (SEC3) has been recently determined to 3.5 Å resolution. To evaluate the actual contribution of individual SAG residues to stabilizing the β–SEC3 complex, as well as to investigate the relationship between the affinity of SAGs for TCR and MHC and their ability to activate T cells, we measured the binding of a set of SEC3 and staphylococcal enterotoxin B (SEB) mutants to soluble recombinant TCR β chain and to the human MHC class II molecule HLA-DR1. Affinities were determined by sedimentation equilibrium and/or surface plasmon detection, while mitogenic potency was assessed using T cells from rearrangement-deficient TCR transgenic mice. We show that there is a clear and simple relationship between the affinity of SAGs for the TCR and their biological activity: the tighter the binding of a particular mutant of SEC3 or SEB to the TCR β chain, the greater its ability to stimulate T cells. We also find that there is an interplay between TCR–SAG and SAG–MHC interactions in determining mitogenic potency, such that a small increase in the affinity of a SAG for MHC can overcome a large decrease in the SAG's affinity for the TCR. Finally, we observe that those SEC3 residues that make the greatest energetic contribution to stabilizing the β–SEC3 complex (“hot spot” residues) are strictly conserved among enterotoxins reactive with mouse Vβ8.2, thereby providing a basis for understanding why SAGs having other residues at these positions show different Vβ-binding specificities.
Details
- Title: Subtitle
- A Mutational Analysis of the Binding of Staphylococcal Enterotoxins B and C3 to the T Cell Receptor β Chain and Major Histocompatibility Complex Class II
- Creators
- Lukas Leder - From the Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850; Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada; the Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844; the Department of Microbiology, University of MinnAndrea Llera - From the Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850; Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada; the Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844; the Department of Microbiology, University of MinnPascal M Lavoie - From the Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850; Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada; the Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844; the Department of Microbiology, University of MinnMarina I Lebedeva - From the Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850; Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada; the Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844; the Department of Microbiology, University of MinnHongmin Li - From the Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850; Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada; the Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844; the Department of Microbiology, University of MinnRafick-Pierre Sékaly - From the Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850; Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada; the Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844; the Department of Microbiology, University of MinnGregory A Bohach - From the Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850; Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada; the Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844; the Department of Microbiology, University of MinnPamala J Gahr - From the Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850; Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada; the Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844; the Department of Microbiology, University of MinnPatrick M Schlievert - From the Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850; Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada; the Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844; the Department of Microbiology, University of MinnKlaus Karjalainen - From the Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850; Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada; the Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844; the Department of Microbiology, University of MinnRoy A Mariuzza - From the Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850; Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada; the Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844; the Department of Microbiology, University of Minn
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.187(6), pp.823-833
- DOI
- 10.1084/jem.187.6.823
- PMID
- 9500785
- PMCID
- PMC2212189
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 03/16/1998
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001116202771
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