Abstract
A three-dimensional model of the complex between an Influenza Hemagglutinin peptide, Ha255−262, and its restricting element, the mouse major histocompatibility complex (MHC) class I molecule, Kk, was built by homology modeling and subsequently refined by simulated annealing and restrained molecular dynamics. Next, three-dimensional models of two different T cell receptors (TCRs) both specific for the Ha255−262/Kk complex were generated based on previously published TCR X-ray structures. Finally, guided by the recently published X-ray structures of ternary TCR/peptide/MHC-I complexes, the TCR models were successfully docked into the Ha255−262/Kk model. We have previously used a systematic and exhaustive panel of 144 single amino acid substituted analogs to analyze both MHC binding and T cell recognition of the parental viral peptide. This large body of experimental data was used to evaluate the models. They were found to account well for the experimentally obtained data, lending considerable support to the proposed models and suggesting a universal docking mode for αβ TCRs to MHC-peptide complexes. Such models may also be useful in guiding future rational experimentation.
References
Townsend, A. and Bodmer, H., Annu. Rev. Immunol., 7 (1989) 601.
Heemels, M.T. and Ploegh, H.L., Annu. Rev. Biochem., 64 (1995) 643.
Batalia, M.A. and Collins E.J., Biopolymers, 43 (1997) 281.
Wilson, I.A. and Garcia, K.C., Curr. Opin. Struct. Biol., 7 (1997) 839.
Chothia, C., Boswell, D.R. and Lesk, A.M., EMBO J., 7 (1988) 3745.
Bentley, G.A., Boulot, G., Karjalainen, K. and Mariuzza, R.A., Science, 267 (1995) 1984.
Fields, B.A., Ober, B., Malchiodi, E.L., Lebedeva, M., Braden, B.C., Ysern, X., Kim, J.-K., Shao, X., Ward, S. and Mariuzza, R.A., Science, 270 (1995) 1821.
Davis, M.M. and Bjorkman, P.J., Nature, 344 (1988) 395.
Garcia, K.C., Degano, M., Stanfield, R.L., Brunmark, A., Jackson, M.R., Peterson, P.E., Teyton, L. and Wilson, I.A., Science, 274 (1996) 209.
Garcia, K.C., Degano, M., Pease, L.R., Huang, M., Peterson, P.A., Teyton, L. and Wilson, I.A., Science, 279 (1998) 1666.
Garboczi, D.N., Ghosh, P., Utz, U., Fan, Q.R., Biddison, W.E. and Wiley, D.C., Nature, 384 (1996) 134.
Ding, Y.H., Smith, K.J., Garboczi, D.N., Utz, U., Biddison, W.E. and Wiley, D.C., Immunity, 8 (1998) 403.
Jorgensen, J.L., Esser, U., Fazekas de St. Groth, B., Reay, P.A. and Davis, M.M., Nature, 355 (1992) 224.
Vasmatzis, G., Cornette, J., Sezerman, U. and DeLisi, C., J. Mol. Biol., 261 (1996) 72.
Sim, B.-C., Travers, B.J. and Gascoigne, N.R., J. Immunol., 159 (1997) 3322.
Stryhn, A., Andersen, P.S., Pedersen, L.O., Svejgaard, A., Holm, A., Thorpe, C.J., Fugger, L., Buus, S. and Engberg, J., Proc. Natl. Acad. Sci. USA, 93 (1996) 10338.
Stryhn, A., Pedersen, L.O., Romme, T., Holm, C.B., Holm, A. and Buus, S., Eur. J. Immunol., 26 (1996) 1911.
Casanova, J.R., Romero, P., Widmann, C., Kourilsky, P. and Maryanski, J.L., J. Exp. Med., 174 (1991) 1371.
Lipman, D.J., Altschul, S.F. and Kececioglu, J.D., Proc. Natl. Acad. Sci. USA, 86 (1989) 4412 (web site: http://www.ibc.wustl.edu/ibc/msa.html).
http://www2.igh-cnrs.fr/bin/align-guess.cgi
Fremont, D.H., Matsumura, M., Stura, E.A., Peterson, P.A. and Wilson, I.A., Science, 257 (1992) 919.
Rognan, D., Molecular modelling of protein-peptide interactions. Application to major histocompatibility complex proteins and design of nonpeptide ligands. Habilitationsschrift, ETH Zürich, 1997.
Pearlman, D.A., Case, D.A., Caldwell, J.C., Ross, W.S., Cheatham III, D.E., Fergusson, D.E., Seibel, G.L., Singh, U.C., Weiner P.K. and Kollman, P.A., AMBER 4.1, University of California, San Francisco, CA, USA, 1995.
Garcia, F., Rognan, D., Lamas, J.R., Marina, M. and López de Castro, J.A., Tissue Antigens, 51 (1998) 1.
Rognan, D., Scapozza, L., Folkers, G. and Daser, A., Biochemistry, 33 (1994) 11476.
Rognan, D., Scapozza, L., Folkers, G. and Daser, A., Proc. Natl. Acad. Sci. USA, 92 (1995) 753.
Rognan, D., Krebs, S., Kuonen, O., Lamas, J.R., López de Castro, J.A. and Folkers, G., J. Comput.-Aided Mol. Design, 11 (1997) 463.
Laskowski, R.A., MacArthur, M.W., Moss, D.S. and Thornton, J.M., J. Appl. Crystallogr., 26 (1993) 9283.
ProsaII v-3.0: http://www.came.sbg.ac.at/
Sippl, M., Proteins Struct. Funct. Genet., 17 (1993) 355.
Collaborative computational project, Number 4: Acta Crystallogr., D50 (1994) 760.
Fremont, D.H., Stura, E.A., Matsumura, M., Peterson, P.A. and Wilson, I.A., Proc. Natl. Acad. Sci. USA, 92 (1995) 2479.
Young, A.C.M., Zhang, W., Sacchettini, J.C. and Nathenson, S.G., Cell, 76 (1994) 39.
Zhang, W., Young, A.C.M., Imarai, M., Nathenson, S.G. and Sacchettini, J.C., Proc. Natl. Acad. Sci. USA, 89 (1992) 8043.
Balendiran, G.K., Solheim, J.C., Yong, A.C.M., Hansen, T.H., Nathenson, S.G. and Sacchettini, J.C., Proc. Natl. Acad. Sci. USA, 94 (1997) 6880.
Speir, J., Garcia, K.C., Brunmark, A., Degano, M., Peterson, P.A., Teyton, L. and Wilson, I.A., Immunity, 8 (1998) 553.
Achour, A., Persson, K., Harris, R.A., Sundbäck, J., Sentman, C.L., Lindqvist, Y., Schneider, G. and Kärre, K., Immunity, 9 (1998) 199.
Bernstein, F.C., Koetzle, T.F., Williams, G.J.B., Meyer Jr., E.F., Brice, M.D., Rodgers, J.M., Kennard, O., Shimanouchi, T. and Tasumi, M., J. Mol. Biol., 112 (1977) 535.
Madden, D.R., Garboczi, D.N. and Wiley, D.C., Cell, 75 (1993) 693.
Housset, D., Mazza, G., Gregoire, C., Piras, C., Malissen, B. and Fontecilla-Camps, J.C., EMBO J., 16 (1997) 4205.
Wang, J.H., Lim, K., Smolyar, A., Teng, M.K., Liu, J.H., Tse, G.D., Liu, J., Hussey, R.E., Chishti, Y., Thomson, C.T., Sweet, R.M., Nathenson, S.G., Chang, H.-C., Sacchettini, J.C. and Reinherz, E.L., EMBO J., 1998 (17) 10.
Dong, T., Boyd, D., Rosenberg, W., Alp, N., Takiguchi, M., McMichael, A. and Rowland-Jones, S., Eur. J. Immunol., 26 (1996) 335.
Mosimann, S., Meleshko, R. and James, M.N.G., Proteins Struct. Funct. Genet., 23 (1995) 301.
Cornell, W.D., Cieplak, P., Bayly, C.I., Gould, I.R., Merz Jr., K.M., Ferguson, D.M., Spellmeyer, D.M., Fox, T., Caldwell, J.W. and Kollman, P.A., J. Am. Chem. Soc., 117 (1995) 5179.
Lozano, J.J., López-de-Briñas, E., Centeno, N.B., Guigó and Sanz, F., J. Comput.-Aided Mol. Design, 11 (1997) 395.
Zamoyska, R., Curr. Opin. Immunol., 10 (1998) 82.
Bjorkman, P.J. and Parham, P., Annu. Rev. Biochem., 59 (1990) 253.
Garcia, K.C., Scott, C.A., Brunmark, A., Carbone, F.R., Peterson, I.A., Wilson, I.A. and Teyton, L., Nature, 384 (1996) 577.
Sant-Angelo, D.B., Waterbury, G., Preston-Hurlburt, P., Yoon, S.T., Medzhitov, R., Hing, S.C. and Janeway Jr., C.A., Immunity, 4 (1996) 367.
Chang, H.-C., Smolyar, A., Spoerl, R., Witte, T., Yao, Y., Goyarts, E.C., Nathenson, S.G. and Reinherz, E.L., J. Mol. Biol., 271 (1997) 278.
Madden, D.R., Gorga, J.C., Strominger, J.L. and Wiley, D.C., Cell, 70 (1992) 1035.
Smith, K.J., Reid, S.W., Harlos, K., McMichael, A.J., Stuart, D.I., Bell, J.I. and Jones, E.Y., Immunity, 4 (1996) 215.
Saper, M.A., Bjorkman, P.J. and Wiley, D.C., J. Mol. Biol., 219 (1991) 277.
Kabat, E.A., Wu, T.T., Reid-Miller, M., Pevey, H.M. and Gotteman, K.S., Sequence of Proteins of Immunological Interest (NIH, Bethesda, MD) ed 5., 1991.
Kraulis, P.J., J. Appl. Crystallogr., 24 (1991) 946.
Merritt, E.A. and Murphy, M.E.P., Acta Crystallogr., D50 (1994) 869.
Nicholls, A., Sharp, K.A. and Honig, B., Proteins Struct. Funct. Genet., 11 (1991) 281.
Islam, S.A. and Sternberg, M.J.E. (1998) PREPI Version 0.95, Biomolecular modelling Laboratory, Imperial Cancer Research Fund, London, U.K. (http://www.icnet.uk/bmm)
http://www.povray.org.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rognan, D., Stryhn, A., Fugger, L. et al. Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. I. Recognition by two αβ T cell receptors. J Comput Aided Mol Des 14, 53–69 (2000). https://doi.org/10.1023/A:1008142830353
Issue Date:
DOI: https://doi.org/10.1023/A:1008142830353