A novel loop domain in superantigens extends their T cell receptor recognition site.
Superantigens (SAGs) interact with host immune receptors to induce a massive release of inflammatory cytokines that can lead to toxic shock syndrome and death. Bacterial SAGs can be classified into five distinct evolutionary groups. Group V SAGs are characterized by the alpha3-beta8 loop, a unique approximately 15 amino acid residue extension that is required for optimal T cell activation. Here, we report the X-ray crystal structures of the group V SAG staphylococcal enterotoxin K (SEK) alone and in complex with the TCR hVbeta5.1 domain. SEK adopts a unique TCR binding orientation relative to other SAG-TCR complexes, which results in the alpha3-beta8 loop contacting the apical loop of framework region 4, thereby extending the known TCR recognition site of SAGs. These interactions are absolutely required for TCR binding and T cell activation by SEK, and dictate the TCR Vbeta domain specificity of SEK and other group V SAGs.
Günther
Sebastian
S
Boston Biomedical Research Institute, Watertown, MA 02472, USA.
Varma
Ashok K
AK
Moza
Beenu
B
Kasper
Katherine J
KJ
Wyatt
Aaron W
AW
Zhu
Penny
P
Rahman
A K M Nur-ur
AK
Li
Yili
Y
Mariuzza
Roy A
RA
McCormick
John K
JK
Sundberg
Eric J
EJ
D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
D001426:Bacterial Proteins; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens