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Molecular Recognition of Diverse Ligands by T-Cell Receptors

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Book cover Epitope Mapping Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 524))

Summary

T-cell receptors (TCRs) are structurally related to antibodies, and also interact with a diverse set of ligands. TCRs recognize foreign peptide antigens displayed by major histocompatibility complex (MHC) molecules and foreign lipid-based antigens presented by CD1. These interactions initiate an immune response through T-cell activation. These critical surveillance and response initiation functions of the adaptive immune system are not perfect, though, as TCR interactions with self antigens can lead to autoimmune disease. Mutated peptides can also be recognized specifically by TCRs, and may be important in tumor immunity. TCRs are also bound specifically by a family of bacterial toxins called superantigens, which over-stimulate the immune system to cause numerous human diseases.

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References

  1. Houghton, A. N. and Guevara-Patino, J. A. (2004) Immune recognition of self in immunity against cancer. J. Clin. Invest. 114, 468–471.

    PubMed  CAS  Google Scholar 

  2. Rosenberg, S. A. (2001) Progress in human tumour immunology and immunotherapy. Nature 411, 380–384.

    Article  PubMed  CAS  Google Scholar 

  3. Rudolph, M. G., Stanfield, R. L., and Wilson, I. A. (2006) How TCRs bind MHCs, peptides, and coreceptors. Ann. Rev. Immunol. 24, 419–466.

    Article  CAS  Google Scholar 

  4. Clements, C. S., Dunstone, M. A., MacDonald, W. A., McCluskey, J., and Rossjohn, J. (2006) Specificity on a knife-edge: the alphabeta T cell receptor. Curr. Opin. Struct. Biol. 16, 787–795.

    Article  PubMed  CAS  Google Scholar 

  5. Hennecke, J., Carfi, A., and Wiley, D. C. (2000) Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1. EMBO J. 19, 5611–5624.

    Article  PubMed  CAS  Google Scholar 

  6. van der Merwe, P. A. and Davis, S. J. (2003) Molecular interactions mediating T cell antigen recognition. Annu. Rev. Immunol. 21, 659–84.

    Article  PubMed  CAS  Google Scholar 

  7. Hahn, M., Nicholson, M. J., Pyrdol, J., and Wucherpfennig, K. W. (2005) Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor. Nat. Immunol. 6, 490–496.

    Article  PubMed  CAS  Google Scholar 

  8. Li, Y., Huang, Y., Lue, J., Quandt, J. A., Martin, R., and Mariuzza, R. A. (2005) Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule. EMBO J. 24, 2968–2979.

    Article  PubMed  CAS  Google Scholar 

  9. He, X. L., Radu, C., Sidney, J., Sette, A., Ward, E. S., and Garcia, K. C. (2002) Structural snapshot of aberrant antigen presentation linked to autoimmunity: the immunodominant epitope of MBP complexed with I-Au. Immunity 17, 83–94.

    Article  PubMed  CAS  Google Scholar 

  10. Deng, L., Langley, R. J., Brown, P. H., Xu, G., Teng, L., Wang, Q., Gonzales, M. I., Callender, G. G., Nishimura, M. I., Topalian, S. L., and Mariuzza, R. A. (2007) Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor. Nat. Immunol. 8, 398–408.

    Article  PubMed  CAS  Google Scholar 

  11. Reinherz, E. L., Tan, K., Tang, L., Kern, P., Liu, J., Xiong, Y., Hussey, R. E., Smolyar, A., Hare, B., Zhang, R., Joachimiak, A., Chang, H. C., Wagner, G., and Wang, J. (1999) The crystal structure of a T cell receptor in complex with peptide and MHC class II. Science 286, 1913–1921.

    Article  PubMed  CAS  Google Scholar 

  12. Borg, N. A., Wun, K. S., Kjer-Nielsen, L., Wilce, M. C., Pellicci, D. G., Koh, R., Besra, G. S., Bharadwaj, M., Godfrey, D. I., McCluskey, J., and Rossjohn, J. (2007) CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 448, 44–49.

    Article  PubMed  CAS  Google Scholar 

  13. Gadola, S. D., Koch, M., Marles-Wright, J., Lissin, N. M., Sheperd, D., Matulis, G., Harlos, K., Villiger, P. M., Stuart, D. I., Jakobsen, B. K., Cerundolo, V., and Jones, E. Y. (2006) Structure and binding kinetics of three different human CD1d-alpha-galactosylceramide-specific T cell receptors. J. Exp. Med. 203, 699–710.

    Article  PubMed  CAS  Google Scholar 

  14. Kjer-Nielsen, L., Borg, N. A., Pellicci, D. G., Beddoe, T., Kostenko, L., Clements, C. S., Williamson, N. A., Smyth, M. J., Besra, G. S., Reid, H. H., Bharadwaj, M., Godfrey, D. I., Rossjohn, J., and McCluskey, J. (2006) A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition. J. Exp. Med. 203, 661–673.

    Article  PubMed  CAS  Google Scholar 

  15. Cantu, C. 3rd, Benlagha, K., Savage, P. B., Bendelac, A., and Teyton, L. (2003) The paradox of immune molecular recognition of alpha-galactosylceramide: low affinity, low specificity for CD1d, high affinity for alpha beta TCRs. J. Immunol. 170, 4673–4682.

    PubMed  CAS  Google Scholar 

  16. McCormick, J. K., Yarwood, J. M., and Schlievert, P. M. (2001) Toxic shock syndrome and bacterial superantigens: an update. Annu. Rev. Microbiol. 55, 77–104.

    Article  PubMed  CAS  Google Scholar 

  17. Sundberg, E. J., Li, Y., and Mariuzza, R. A. (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, 36–44.

    Article  PubMed  CAS  Google Scholar 

  18. Li, H., Llera A., Tsuchiya, D., Leder, L., Ysern, X., Schlievert, P. M., Karjalainen, K., and Mariuzza, R. A. (1998) Three-dimensional structure of the complex between a T cell receptor beta chain and the superantigen staphylococcal enterotoxin B. Immunity 9, 807–816.

    Article  PubMed  CAS  Google Scholar 

  19. Fields, B. A., Malchiodi, E. L., Li, H., Ysern, X., Stauffacher, C. V., Schlievert, P. M., Karjalainen, K., and Mariuzza, R. A. (1996) Crystal structure of a T-cell receptor beta-chain complexed with a superantigen. Nature 384, 188–192.

    Article  PubMed  CAS  Google Scholar 

  20. Sundberg, E. J., Li, H., Llera, A. S., McCormick, J. K., Tormo, J., Schlievert, P. M., Karjalainen, K., and Mariuzza, R. A. (2002) Structures of two streptococcal superantigens bound to TCR beta chains reveal diversity in the architecture of T cell signaling complexes. Structure 10, 687–699.

    Article  PubMed  CAS  Google Scholar 

  21. Günther, S., Varma, A. K., Moza, B., Kasper, K. J., Wyatt, A. W., Zhu, P., Rahman, A. K., Li, Y., Mariuzza, R. A., McCromick, J. K., and Sundberg, E. J. (2007) A novel loop domain in superantigens extends their T cell receptor recognition site. J. Mol. Biol. 371, 210–221.

    Article  PubMed  Google Scholar 

  22. Moza, B., Buonpane, R. A., Zhu, P., Herfst, C. A., Rahman, A. K., McCormick, J. K., Kranz, D. M., and Sundberg, E. J. (2006) Long-range cooperative binding effects in a T cell receptor variable domain. Proc. Natl. Acad. Sci. USA 103, 9867–9872.

    Article  PubMed  CAS  Google Scholar 

  23. Buonpane, R. A., Moza, B., Sundberg, E. J., and Kranz, D. M. (2005) Characterization of T cell receptors engineered for high affinity against toxic shock syndrome toxin-1. J. Mol. Biol. 353, 308–321.

    Article  PubMed  CAS  Google Scholar 

  24. Rahman, A. K., Herfst, C. A., Moza, B., Shames, S. R., Chau, L. A., Bueno, C., Madrenas, J., Sundberg, E. J., and McCormick, J. K. (2006) Molecular basis of TCR selectivity, cross-reactivity, and allelic discrimination by a bacterial superantigen: integrative functional and energetic mapping of the SpeC-Vbeta2.1 molecular interface. J. Immunol. 177, 8595–8603.

    PubMed  Google Scholar 

  25. Kim, J., Urban, R. G., Strominger, J. L., and Wiley, D. C. (1994) Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1. Science 266, 1870–1874.

    Article  PubMed  CAS  Google Scholar 

  26. Jardetzky, T. S., Brown, J. H., Gorga, J. C., Stern, L. J., Urban, R. G., Chi, Y. I., Stauffacher, C., Strominger, J. L., and Wiley, D. C. (1994) Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen. Nature 368, 711–718.

    Article  PubMed  CAS  Google Scholar 

  27. Li, Y., Li, H., Dimasi, N., McCormick, J. K., Martin, R., Schuck, P., Schlievert, P. M., and Mariuzza, R. A. (2001) Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II. Immunity 14, 93–104.

    Article  PubMed  CAS  Google Scholar 

  28. Fernandez, M. M., Guan, R., Swaminathan, C. P., Malchiodi, E. L., and Mariuzza, R. A. (2006) Crystal structure of staphylococcal enterotoxin I (SEI) in complex with a human major histocompatibility complex class II molecule. J. Biol. Chem. 281, 25356–25364.

    Article  PubMed  CAS  Google Scholar 

  29. Moza, B., Varma, A. K., Buonpane, R. A., Zhu, P., Herfst, C. A., Nicholson, M. J., Wilbuer, A. K., Seth, N. P., Wucherpfennig, K. W., McCormick, J. K., Kranz, D. M., and Sundberg, E. J. (2007) Structural basis of T cell receptor specificity and activation by the bacterial superantigen TSST-1. EMBO J. 26, 1187–1197.

    Article  PubMed  CAS  Google Scholar 

  30. Andersen, P. S., Lavoie, P. M., Sékaly, R. P., Churchill, H., Kranz, D. M., Schlievert, P. M., Karjalainen, K. and Mariuzza, R. A. (1999) Role of the T cell receptor alpha chain in stabilizing TCR-superantigen- MHC class II complexes. Immunity 10, 473–483.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Eric J. Sundberg .

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Sundberg, E.J. (2009). Molecular Recognition of Diverse Ligands by T-Cell Receptors. In: Schutkowski, M., Reineke, U. (eds) Epitope Mapping Protocols. Methods in Molecular Biology™, vol 524. Humana Press. https://doi.org/10.1007/978-1-59745-450-6_25

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  • DOI: https://doi.org/10.1007/978-1-59745-450-6_25

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-934115-17-6

  • Online ISBN: 978-1-59745-450-6

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