So many ways of getting in the way: diversity in the molecular architecture of superantigen-dependent T-cell signaling complexes.
Superantigens (SAGs) elicit massive T-cell proliferation through simultaneous interaction with MHC and TCR molecules. SAGs have been implicated in toxic shock syndrome and food poisoning, and they may also play a pathogenic role in autoimmune diseases. The best-characterized group of SAGs are the pyrogenic bacterial SAGs, which utilize a high degree of genetic variation on a common structural scaffold to achieve a wide range of MHC-binding and T-cell-stimulating effects while assisting pathogen evasion of the adaptive immune response. Several new structures of SAG-MHC and SAG-TCR complexes have significantly increased understanding of the molecular bases for high-affinity peptide/MHC binding by SAGs and for TCR Vbeta domain specificity of SAGs. Using the currently available SAG-MHC and SAG-TCR complex structures, models of various trimolecular MHC-SAG-TCR complexes may be constructed that reveal wide diversity in the architecture of SAG-dependent T-cell signaling complexes, which nevertheless may result in similar signaling outcomes.
Sundberg
Eric J
EJ
Center for Advanced Research in Biotechnology, WM Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850, USA.
Li
Yili
Y
Mariuzza
Roy A
RA
D000483:Alleles; D000818:Animals; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D018089:Superantigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D018089:Superantigens