Structures of two streptococcal superantigens bound to TCR beta chains reveal diversity in the architecture of T cell signaling complexes.
Superantigens (SAGs) crosslink MHC class II and TCR molecules, resulting in an overstimulation of T cells associated with human disease. SAGs interact with several different surfaces on MHC molecules, necessitating the formation of multiple distinct MHC-SAG-TCR ternary signaling complexes. Variability in SAG-TCR binding modes could also contribute to the structural heterogeneity of SAG-dependent signaling complexes. We report crystal structures of the streptococcal SAGs SpeA and SpeC in complex with their corresponding TCR beta chain ligands that reveal distinct TCR binding modes. The SpeC-TCR beta chain complex structure, coupled with the recently determined SpeC-HLA-DR2a complex structure, provides a model for a novel T cell signaling complex that precludes direct TCR-MHC interactions. Thus, highly efficient T cell activation may be achieved through structurally diverse strategies of TCR ligation.
Sundberg
Eric J
EJ
Center for Advanced Research in Biotechnology, W.M. Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850, USA.
Li
Hongmin
H
Llera
Andrea S
AS
McCormick
John K
JK
Tormo
José
J
Schlievert
Patrick M
PM
Karjalainen
Klaus
K
Mariuzza
Roy A
RA
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005098:Exotoxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005802:Genes, MHC Class II; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013297:Streptococcus pyogenes / Q000737:chemistry*; D018089:Superantigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism
D001426:Bacterial Proteins; D005098:Exotoxins; D008565:Membrane Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; C027951:erythrogenic toxin