title: A novel loop domain in superantigens extends their T cell receptor recognition site.
abstract: 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.
authors.affiliation: Boston Biomedical Research Institute, Watertown, MA 02472, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Günther
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Varma
authors.forename: Beenu
authors.initials: B
authors.lastname: Moza
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Kasper
authors.forename: Aaron W
authors.initials: AW
authors.lastname: Wyatt
authors.forename: Penny
authors.initials: P
authors.lastname: Zhu
authors.forename: A K M Nur-ur
authors.initials: AK
authors.lastname: Rahman
authors.forename: Yili
authors.initials: Y
authors.lastname: Li
authors.forename: Roy A
authors.initials: RA
authors.lastname: Mariuzza
authors.forename: John K
authors.initials: JK
authors.lastname: McCormick
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sundberg
mesh_terms: 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
chemical_list: D001426:Bacterial Proteins; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens