TY - JOUR
T1 - Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1
AU - Moza, Beenu
AU - Varma, Ashok K.
AU - Buonpane, Rebecca A.
AU - Zhu, Penny
AU - Herfst, Christine A.
AU - Nicholson, Melissa J.
AU - Wilbuer, Anne Kathrin
AU - Seth, Nilufer P.
AU - Wucherpfennig, Kai W.
AU - McCormick, John K.
AU - Kranz, David M.
AU - Sundberg, Eric J.
PY - 2007/2/21
Y1 - 2007/2/21
N2 - Superantigens (SAGs) bind simultaneously to major histocompatibility complex (MHC) and T-cell receptor (TCR) molecules, resulting in the massive release of inflammatory cytokines that can lead to toxic shock syndrome (TSS) and death. A major causative agent of TSS is toxic shock syndrome toxin-1 (TSST-1), which is unique relative to other bacterial SAGs owing to its structural divergence and its stringent TCR specificity. Here, we report the crystal structure of TSST-1 in complex with an affinity-matured variant of its wild-type TCR ligand, human T-cell receptor β chain variable domain 2.1. From this structure and a model of the wild-type complex, we show that TSST-1 engages TCR ligands in a markedly different way than do other SAGs. We provide a structural basis for the high TCR specificity of TSST-1 and present a model of the TSST-1-dependent MHC-SAG-TCR T-cell signaling complex that is structurally and energetically unique relative to those formed by other SAGs. Our data also suggest that protein plasticity plays an exceptionally significant role in this affinity maturation process that results in more than a 3000-fold increase in affinity.
AB - Superantigens (SAGs) bind simultaneously to major histocompatibility complex (MHC) and T-cell receptor (TCR) molecules, resulting in the massive release of inflammatory cytokines that can lead to toxic shock syndrome (TSS) and death. A major causative agent of TSS is toxic shock syndrome toxin-1 (TSST-1), which is unique relative to other bacterial SAGs owing to its structural divergence and its stringent TCR specificity. Here, we report the crystal structure of TSST-1 in complex with an affinity-matured variant of its wild-type TCR ligand, human T-cell receptor β chain variable domain 2.1. From this structure and a model of the wild-type complex, we show that TSST-1 engages TCR ligands in a markedly different way than do other SAGs. We provide a structural basis for the high TCR specificity of TSST-1 and present a model of the TSST-1-dependent MHC-SAG-TCR T-cell signaling complex that is structurally and energetically unique relative to those formed by other SAGs. Our data also suggest that protein plasticity plays an exceptionally significant role in this affinity maturation process that results in more than a 3000-fold increase in affinity.
KW - Protein-protein interaction
KW - Superantigen
KW - Surface plasmon resonance
KW - T-cell activity
KW - X-ray crystallography
UR - http://www.scopus.com/inward/record.url?scp=33847209552&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847209552&partnerID=8YFLogxK
U2 - 10.1038/sj.emboj.7601531
DO - 10.1038/sj.emboj.7601531
M3 - Article
C2 - 17268555
AN - SCOPUS:33847209552
SN - 0261-4189
VL - 26
SP - 1187
EP - 1197
JO - EMBO Journal
JF - EMBO Journal
IS - 4
ER -