Journal of Computer-Aided Molecular Design

, Volume 16, Issue 4, pp 229–243 | Cite as

Recovery of known T-cell epitopes by computational scanning of a viral genome

Article

Abstract

A new computational method (EpiDock) is proposed for predicting peptide binding to class I MHC proteins, from the amino acid sequence of any protein of immunological interest. Starting from the primary structure of the target protein, individual three-dimensional structures of all possible MHC-peptide (8-, 9- and 10-mers) complexes are obtained by homology modelling. A free energy scoring function (Fresno) is then used to predict the absolute binding free energy of all possible peptides to the class I MHC restriction protein. Assuming that immunodominant epitopes are usually found among the top MHC binders, the method can thus be applied to predict the location of immunogenic peptides on the sequence of the protein target. When applied to the prediction of HLA-A*0201-restricted T-cell epitopes from the Hepatitis B virus, EpiDock was able to recover 92% of known high affinity binders and 80% of known epitopes within a filtered subset of all possible nonapeptides corresponding to about one tenth of the full theoretical list.

The proposed method is fully automated and fast enough to scan a viral genome in less than an hour on a parallel computing architecture. As it requires very few starting experimental data, EpiDock can be used: (i) to predict potential T-cell epitopes from viral genomes (ii) to roughly predict still unknown peptide binding motifs for novel class I MHC alleles.

antigen epitope prediction free energy scoring homology modelling major histocompatibility complex threading 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Heemels, M.T. and Ploegh, H.L., Annu. Rev. Biochem., 64 (1995) 643.Google Scholar
  2. 2.
    Pamer, E. and Cresswell, P., Annu. Rev. Immunol., 16 (1998) 323.Google Scholar
  3. 3.
    Cresswell, P. and Lanzavecchia, A., Curr. Opin. Immunol., 13 (2001) 11.Google Scholar
  4. 4.
    Rock, K.L., Gramm, C., Rothstein, L., Clark, K., Stein, R., Dick, L., Hwang, D. and Goldberg, A.L., Cell, 78 (1994) 761.Google Scholar
  5. 5.
    Neefjes, J.J., Momburg, F. and Hammerling, G.J., Science, 261 (1993) 769.Google Scholar
  6. 6.
    Daniel, S., Brusic, V., Caillat-Zucman, S., Petrovsky, N., Harrison, L., Riganelli, D., Sinigaglia, F., Gallazzi, F., Hammer, J. and van Endert, P.M., J. Immunol., 161 (1998) 617.Google Scholar
  7. 7.
    Rammensee, H., Bachmann, J., Emmerich, N.P., Bachor, O.A. and Stevanovic, S., Immunogenetics, 50 (1999) 213.Google Scholar
  8. 8.
    Kubo, R.T., Sette, A., Grey, H.M., Appella, E., Sakaguchi, K., Zhu, N.Z., Arnott, D., Sherman, N., Shabanowitz, J., Michel, H., Bodnar, W.M., Davis, T.A. and Hunt, D.F., J. Immunol., 152 (1994) 3913Google Scholar
  9. 9.
    Sette, A., Vitiello, A., Reherman, B., Fowler, P., Nayersina, R., Kast, W.M., Melief, C.J., Oseroff, C., Yuan, L. and Ruppert, J.J., Immunol., 153 (1994) 5586.Google Scholar
  10. 10.
    Sette, A., Sidney, J., del Guercio, M.F., Southwood, S., Ruppert, J., Dahlberg, C., Grey, H.M. and Kubo, R.T., Mol. Immunol., 31 (1994) 813.Google Scholar
  11. 11.
    van der Burg, S.H., Visseren, M.J., Brandt, R.M., Kast, W.M. and Melief, C.J., J. Immunol., 156 (1996) 3308.Google Scholar
  12. 12.
    Schirle, M., Weinschenk, T. and Stevanovic, S., J. Immunol. Meth., 257 (2001) 1.Google Scholar
  13. 13.
    Meister, G.E., Roberts, C.G., Berzofsky, J.A. and De Groot, A.S., Vaccine, 13 (1995) 581.Google Scholar
  14. 14.
    D'Amaro, J., Houbiers, J.G., Drijfhout, J.W., Brandt, R.M., Schipper, R., Bavinck, J.N., Melief, C.J. and Kast, W.M., Hum. Immunol., 43 (1995) 13.Google Scholar
  15. 15.
    Gulukota, K., Sidney, J., Sette, A. and DeLisi, C., J. Mol. Biol., 267 (1997) 1258.Google Scholar
  16. 16.
    Milik, M., Sauer, D., Brunmark, A.P., Yuan, L., Vitiello, A., Jackson, M.R., Peterson, P.A., Skolnick, J. and Glass, C.A., Nat. Biotechnol., 16 (1998) 753.Google Scholar
  17. 17.
    Adams, H.P. and Koziol, J.A., J. Immunol. Meth., 185 (1995) 181.Google Scholar
  18. 18.
    Parker, K.C., Bednarek, M.A. and Coligan, J.E., J. Immunol., 152 (1994) 163.Google Scholar
  19. 19.
    Stryhn, A., Pedersen, L.O., Romme, T., Holm, C.B., Holm, A. and Buus, S., Eur. J. Immunol., 26 (1996) 1911.Google Scholar
  20. 20.
    Fremont, D.H., Stura, E.A., Matsumura, M., Peterson, P.A. and Wilson, I.A., Proc. Natl. Acad. Sci. USA, 92 (1995) 2479.Google Scholar
  21. 21.
    Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N. and Bourne, P.E., Nucleic Acids Res., 28 (2000) 235.Google Scholar
  22. 22.
    Batalia, M.A. and Collins, E.J., Biopolymers, 43 (1997) 281.Google Scholar
  23. 23.
    Madden, D.R., Gorga, J.C., Strominger, J.L. and Wiley, D.C., Cell, 70 (1992) 1035.Google Scholar
  24. 24.
    Guo, H., Madden, D., Silver, M., Jardetzky, T., Gorga, J., Strominger, J. and Wiley, D., Proc. Natl. Acad. Sci. USA, 90 (1993) 8053.Google Scholar
  25. 25.
    Ruppert, J., Sidney, J., Celis, E., Kubo, R., Grey, H. and Sette, A., Cell, 10 (1993) 929.Google Scholar
  26. 26.
    Madden, D.R., Garboczi, D.N. and Wiley, D.C., Cell, 75 (1993) 693.Google Scholar
  27. 27.
    Saper, M.A., Bjorkman, P.J. and Wiley, D.C., J. Mol. Biol., 75 (1991) 693.Google Scholar
  28. 28.
    Falk, K., Rotzschke, 0., Stevanovic, S., Jung, G. and Rammensee, H.-G., Nature, 351 (1991) 290.Google Scholar
  29. 29.
    Rognan, D., Scapozza, L., Folkers, G. and Daser, A., Biochemistry, 33 (1994) 11476.Google Scholar
  30. 30.
    Altuvia, Y., Sette, A., Sidney, J., Southwood, S. and Margalit, H., Hum. Immunol., 58 (1997) 1.Google Scholar
  31. 31.
    Schueler-Furman, O., Altuvia, Y., Sette, A. and Margalit, H., Protein Sci., 9 (2000) 1838.Google Scholar
  32. 32.
    Zeng, J., Treutlein, H.R. and Rudy, G.B., J. Comput. Aid. Mol. Des., 15 (2001) 573.Google Scholar
  33. 33.
    Doytchinova, I.A. and Flower, D.R., J. Med. Chem., 44 (2001) 3572.Google Scholar
  34. 34.
    Rognan, D., Lauemoller, S.L., Holm, A., Buus, S. and Tschinke, V., J. Med. Chem, 42 (1999) 4650.Google Scholar
  35. 35.
    Logean, A., Sette, A. and Rognan, D., Bioorg. Med. Chem. Lett., 11 (2001) 675.Google Scholar
  36. 36.
    TRIPOS Assoc., I., release 6.72.Google Scholar
  37. 37.
    Case, D.A., Pearlman, D.A., Caldwell, J.W., Cheatham III, D.E., Ross, W.S., Simmerling, C.L., Darden, T.A., Merz, K.M., Stanton, R.V., Cheng, A.L., Vincent, J.J., Crowley, M., Tsui, V., Radmer, R.J., Duan, Y., Pitera, J., Massova, I., Seibel, G.L., Singh, V.C., Weiner, P.K. and Kollman, P.A. (1999) Amber 6.0, University of California, San Francisco.Google Scholar
  38. 38.
    Jardetzky, T.S., Lane, W.S., Robinson, R.A., Madden, D.R. and Wiley, D.C., Nature, 353 (1991) 326.Google Scholar
  39. 39.
    Lamas, J.R., Paradela, A., Roncal, F. and Lopez de Castro, J.A., Arthritis Rheumatism, 42 (1999) 1975.Google Scholar
  40. 40.
    Dedier, S., Reinelt, S., Reitinger, T., Folkers, G. and Rognan, D., J. Biol. Chem., 275 (2000) 27055.Google Scholar
  41. 41.
    Fairchild, P.J., J. Pept. Sci., 4 (1998) 182.Google Scholar
  42. 42.
    Guo, H.C., Jardetzky, T.S., Garrett, T.P.J., Lane, W.S., Strominger, J.L. and Wiley, D.C., Nature, 360 (1992) 364.Google Scholar
  43. 43.
    Garcia, K.C., Degano, M., Pease, L.R., Huang, M., Peterson, P.A., Teyton, L. and Wilson, I.A., Science, 279 (1998) 1666.Google Scholar
  44. 44.
    Garboczi, D.N., Ghosh, P., Utz, U., Fan, Q.R., Biddison, W.E. and Wiley, D.C., Nature, 384 (1996) 134.Google Scholar
  45. 45.
    Buus, S., Curr. Opin. Immunol., 11 (1999) 209.Google Scholar
  46. 46.
    Lamas, J.R., Brooks, J.M., Galocha, B., Rickinson, A.B. and Lopez de Castro, J.A., Int. Immunol., 10 (1998) 259.Google Scholar
  47. 47.
    Luu, T., Pham, S. and Deshpande, S., Int. J. Pept. Protein Res., 47 (1996) 91.Google Scholar
  48. 48.
    Dedier, S., Reinelt, S., Rion, S., Folkers, G. and Rognan, D., J. Immunol. Meth., 255 (2001) 57.Google Scholar
  49. 49.
    McKinney, D.M., Skvoretz, R., Qin, M., Ishioka, G. and Sette, A., J. Immunol. Meth., 237 (2000) 105.Google Scholar
  50. 50.
    Davenport, N.P., Smith, K.J., Barouch, D., Reid, S.W., Bodnar, W.M., Willis, A.M., Hunt, D.F. and A.V.S., H., J. Exp. Med., 185 (1997) 367.Google Scholar
  51. 51.
    Holzhutter, H.G., Frommel, C. and Kloetzel, P.M., J. Mol. Biol., 286 (1999) 1251.Google Scholar
  52. 52.
    Kesimir, C., Nussbaum, A.K., Schild, H., Detours, V., Brunak, S. Protein Eng., 15 (2002) 287; http://www.cbs.dtu.dk/services/NetChop/Google Scholar
  53. 53.
    Nussbaum, A.K., Kuttler, C., Hadeler, K.P., Rammensee, H.G. and Schild, H. Immunogenetics, 53 (2001) 87.Google Scholar
  54. 54.
    Brusic, V., van Endert, P., Zeleznikow, J., Daniel, S., Hammer, J. and Petrovsky, N., In Silico Biol., 1 (1999) 109.Google Scholar
  55. 55.
    Cornell, W.D., Cieplak, P., Bayly, C.I., Gould, I.R., Merz, K.M., Jr., Ferguson, D.M., Spellmeyer, D.C., Fox, T., Caldwell, J.W. and Kollman, P.A., J. Am. Chem. Soc., 117 (1995) 5179.Google Scholar
  56. 56.
    Nicholls, A., Sharp, K.A. and Honig, B., Proteins Struct. Funct. Genet., 11 (1991) 281.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  1. 1.Bioinformatic GroupLaboratoire de Pharmacochimie de la Communication Cellulaire, UMR CNRS 7081IllkirchFrance
  2. 2.Department of Applied BiosciencesSwiss Federal Institute of TechnologyZürichSwitzerland

Personalised recommendations