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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 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...

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Autores principales: Leder, Lukas, Llera, Andrea, Lavoie, Pascal M., Lebedeva, Marina I., Li, Hongmin, Sékaly, Rafick-Pierre, Bohach, Gregory A., Gahr, Pamala J., Schlievert, Patrick M., Karjalainen, Klaus, Mariuzza, Roy A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212189/
https://www.ncbi.nlm.nih.gov/pubmed/9500785
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author Leder, Lukas
Llera, Andrea
Lavoie, Pascal M.
Lebedeva, Marina I.
Li, Hongmin
Sékaly, Rafick-Pierre
Bohach, Gregory A.
Gahr, Pamala J.
Schlievert, Patrick M.
Karjalainen, Klaus
Mariuzza, Roy A.
author_facet Leder, Lukas
Llera, Andrea
Lavoie, Pascal M.
Lebedeva, Marina I.
Li, Hongmin
Sékaly, Rafick-Pierre
Bohach, Gregory A.
Gahr, Pamala J.
Schlievert, Patrick M.
Karjalainen, Klaus
Mariuzza, Roy A.
author_sort Leder, Lukas
collection PubMed
description 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.
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spelling pubmed-22121892008-04-16 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 Leder, Lukas Llera, Andrea Lavoie, Pascal M. Lebedeva, Marina I. Li, Hongmin Sékaly, Rafick-Pierre Bohach, Gregory A. Gahr, Pamala J. Schlievert, Patrick M. Karjalainen, Klaus Mariuzza, Roy A. J Exp Med Article 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. The Rockefeller University Press 1998-03-16 /pmc/articles/PMC2212189/ /pubmed/9500785 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Leder, Lukas
Llera, Andrea
Lavoie, Pascal M.
Lebedeva, Marina I.
Li, Hongmin
Sékaly, Rafick-Pierre
Bohach, Gregory A.
Gahr, Pamala J.
Schlievert, Patrick M.
Karjalainen, Klaus
Mariuzza, Roy A.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort mutational analysis of the binding of staphylococcal enterotoxins b and c3 to the t cell receptor β chain and major histocompatibility complex class ii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212189/
https://www.ncbi.nlm.nih.gov/pubmed/9500785
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