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
Houghton, A. N. and Guevara-Patino, J. A. (2004) Immune recognition of self in immunity against cancer. J. Clin. Invest. 114, 468–471.
Rosenberg, S. A. (2001) Progress in human tumour immunology and immunotherapy. Nature 411, 380–384.
Rudolph, M. G., Stanfield, R. L., and Wilson, I. A. (2006) How TCRs bind MHCs, peptides, and coreceptors. Ann. Rev. Immunol. 24, 419–466.
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.
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.
van der Merwe, P. A. and Davis, S. J. (2003) Molecular interactions mediating T cell antigen recognition. Annu. Rev. Immunol. 21, 659–84.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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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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