A Novel Loop Domain in Superantigens Extends Their T Cell Receptor Recognition Site

Journal Article · Mon Jan 01 04:00:00 EST 2007 · Journal of Molecular Biology

DOI:https://doi.org/10.1016/j.jmb.2007.05.038· OSTI ID:929985

Gunther, S; Varma, A; Moza, B; Kasper, K; Wyatt, A; Zhu, P; Nur-ur Rahman, A; Li, Y; Mariuzza, R

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 {alpha}3-{beta}8 loop, a unique {approx}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 hV{beta}5.1 domain. SEK adopts a unique TCR binding orientation relative to other SAG-TCR complexes, which results in the {alpha}3-{beta}8 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 V{beta} domain specificity of SEK and other group V SAGs.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 929985
• Report Number(s): BNL--80594-2008-JA
• Journal Information: Journal of Molecular Biology, Journal Name: Journal of Molecular Biology Vol. 371; ISSN JMOBAK; ISSN 0022-2836
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
AMINO ACIDS
ANTIGENS
COMPLEXES
CRYSTAL STRUCTURE
DEATH
INTERACTIONS
LYMPHOKINES
ORIENTATION
RECEPTORS
RESIDUES
SPECIFICITY
national synchrotron light source