Chapter 16 : Countermeasures against Superantigens: Structure-Based Design of Bispecific Receptor Mimics

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Countermeasures against Superantigens: Structure-Based Design of Bispecific Receptor Mimics, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815844/9781555814243_Chap16-1.gif /docserver/preview/fulltext/10.1128/9781555815844/9781555814243_Chap16-2.gif


Superantigens (SAgs) are a family of highly potent immunostimulatory proteins produced by bacteria or viruses. The family includes many proteins that may be unrelated by sequence or structure and yet share the ability to bypass the mechanisms of conventional antigen processing and trigger excessive activation of T cells. The massive lymphokine release by the activated cells within hours and the excessive T-cell proliferation in 2 to 3 days could ultimately lead to an immunosuppressive state and favor the microbe. Human diseases caused by microbes that utilize SAgs as their major virulence factors are characterized by fever and shock. The enterotoxins A-1 are thought to be the causative agents in 33% of all food-poisoning cases and are the most frequent cause of hospital-acquired infections. Presently, the treatment of superantigen-mediated infections is limited to the administration of antibiotics and handling of the state of shock. Conventional antigens are phagocytosed by antigenpresenting cells (APCs) and are processed into discrete peptides. The SAgs of and share a common architecture despite their significant difference in sequence. SAgs are globular proteins of 22 to 29 kDa, composed of two domains, amino- and carboxy-terminal, that are separated by a long, solvent-accessible α- helix spanning the center of the molecule. The T-cell receptor is a transmembrane heterodimer, composed of α- and β-chains. Each chain is composed of constant (C) and variable (V) regions.

Citation: Gupta G, Kunkel M. 2007. Countermeasures against Superantigens: Structure-Based Design of Bispecific Receptor Mimics, p 245-254. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch16
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Arcus, V. L.,, T. Proft,, J. A. Sigrell,, H. M. Baker,, J. D. Fraser, and, E. N. Baker. 2000. Conservation and variation in superantigen structure and activity highlighted by the three-dimensional structures of two new superantigens from Streptococcus pyogenes. J. Mol. Biol. 299(1): 157168
2. Baker, M. D., and, K. R. Acharya. 2004. Superantigens: structure-function relationships. Int. J. Med. Microbiol. 293(7–8): 529537.
3. Chesney P. J.,, M. S. Bergdoll,, J. P. Davis, and, J. M. Vergeront. 1984. The disease spectrum, epidemiology, and etiology of toxic-shock syndrome. Annu. Rev. Microbiol. 38: 315338.
4. Emori, T. G., and, R. P. Gaynes. 1993. An overview of nosocomial infections, including the role of the microbiology laboratory. Clin. Microbiol. Rev. 6(4): 428442.
5. Gronenborn, A. M., and, G. M. Clore. 1993. Identification of the contact surface of a streptococcal protein G domain complexed with a human Fc fragment. J. Mol. Biol. 233(3): 331335.
6. Hong-Geller, E.,, M. Möllhoff,, P. R. Shiflett, and, G. Gupta. 2004. Design of chimeric receptor mimics with different TcRVβ isoforms. J. Biol. Chem. 279: 56765684.
7. Kappler, J.,, B. Kotzin,, L. Herron,, E. W. Gelfand,, R. D. Bigler,, A. Boylston,, S. Carrel,, D. N. Posnett,, Y. Choi, and, P. Marrack. 1989. V beta-specific stimulation of human T cells by staphylococcal toxins. Science 244: 811813.
8. Kieke, M. C.,, E. Sundberg,, E. V. Shusta,, R. A. Mariuzza,, K. D. Wittrup, and, D. M. Kranz. 2001. High affinity T cell receptors from yeast display libraries block T cell activation by superantigens. J. Mol. Biol. 307(5): 13051315.
9. Kotzin, B. L.,, D. Y. Leung,, J. Kappler, and, P. Marrack. 1993. Superantigens and their potential role in human disease. Adv. Immunol. 54: 99166.
10. Laurence, J.,, A. S. Hodtsev, and, D. N. Posnett. 1992. Superantigen implicated in dependence of HIV-1 replication in T cells on TCR V beta expression. Nature 358(6383): 255259.
11. Leder, L.,, A. Llera,, P. M. Lavoie,, M. I. Lebedeva,, H. Li,, R. P. Sekaly,, G. A. Bohach,, P. J. Gahr,, P. M. Schlievert,, K. Karjalainen, and, R. A. Mariuzza. 1998. A mutational analysis of the binding of staphylococcal enterotoxins B and C3 to the T cell receptor beta chain and major histocompatibility complex class II. J. Exp. Med. 187(6): 823833.
12. Lehnert, N. M.,, D. L. Allen,, B. L. Allen,, P. Catasti,, P. R. Shiflett,, M. Chen,, B. E. Lehnert, and, G. Gupta. 2001. Structure-based design of a bispecific receptor mimic that inhibits T cell responses to a superantigen. Biochemistry 40: 42224228.
13. Marrack, P., and, J. Kapler. 1990. The staphylococcal enterotoxins and their relatives. Science 248: 705711.
14. Möllhoff, M.,, H. B. Vander Zanden,, P. R. Shiflett, and, G. Gupta. 2005. Modeling of receptor mimics that inhibit superantigen pathogenesis. J. Mol. Recognit. 18: 7383.
15. Murzin, A. G. 1993. Can homologous proteins evolve different enzymatic activities? Trends Biochem. Sci. 18(11): 403405.
16. Pearlman, D. A.,, D. A. Case,, J. W. Caldwell,, W. S. Ross,, T. E. Cheatham,, S. DeBolt,, D. Ferguson,, G. Seibel, and, P. Kollman. 1995. AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules. Com. Phys. Comm. 91(1): 141.
17. Petersson, K.,, G. Forsberg, and, B. Walse. 2004. Interplay between superantigens and immunoreceptors. Scand. J. Immunol. 59(4): 345355.
18. Schiffenbauer, J.,, H. M. Johnson,, E. J. Butfiloski,, L. Wegrzyn, and, J. M. Soos. 1993. Staphylococcal enterotoxins can reactivate experimental allergic encephalomyelitis. Proc. Natl. Acad. Sci. USA 90(18): 85438546.
19. Sundberg, E. J.,, Y. Li, and, R. A. Mariuzza. 2002. So many ways of getting in the way: diversity in the molecular architecture of superantigen-dependent T-cell signaling complexes. Curr. Opin. Immunol. 14(1): 3644.
20. Wikstrom, M.,, T. Drakenberg,, S. Forsen,, U. Sjobring, and, L. Bjorck. 1994. Three-dimensional solution structure of an immunoglobulin light chain-binding domain of protein L. Comparison with the IgG-binding domains of protein G. Biochemistry 33(47): 1401114017.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error