Skip to main content

Computational Immunology: HLA-peptide Binding Prediction

  • Chapter
  • 2932 Accesses

Abstract

HLA molecules are immune proteins that play an important role in T-cell mediated immune response. They bind short 8-20 residues long peptides from antigen proteins to induce immune response. Therefore, the binding of short antigen peptides to HLA molecules is the rate limiting step in T-cell mediated immune response. Several constructs of overlapping short peptides can be designed from a given protein antigen sequence. The number of overlapping peptides is large for systematic experimental testing. Moreover, HLA molecules are highly polymorphic and more than 1500 HLA alleles are known among the human population. Thus, the binding of short peptides to HLA is combinatorial and specific. The binding can be studied using expensive and laborious competitive binding assays. Alternatively, prediction of peptide binding to HLA molecules is highly useful. Efficient prediction models enable systematic scanning of candidate peptides in an effective manner. Here, we describe some commonly used prediction models.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adams, H.P. and Koziol, J.A. (1995) Prediction of binding to MHC class I molecules. J Immunol Methods185(2), 181–90.

    Article  CAS  Google Scholar 

  • Altuvia, Y., Schueler, O., et al. (1995) Ranking potential binding peptides to MHC molecules by a computational threading approach. JMol Biol249(2), 244–50.

    Article  CAS  Google Scholar 

  • Altuvia, Y., Sette, A., et al. (1997) A structure-based algorithm to predict potential binding peptides to MHC molecules with hydrophobic binding pockets. Hum Immunol58(1), 1–11.

    Article  PubMed  CAS  Google Scholar 

  • Batalia, M.A. and Collins, E.J. (1997) Peptide binding by class I and class II MHC molecules. Biopolymers43(4), 281–302.

    Article  PubMed  CAS  Google Scholar 

  • Berman, H.M., Westbrook, I, et al. (2000) The Protein Data Bank. Nucleic Acids Res28(1), 235–42.

    Article  PubMed  CAS  Google Scholar 

  • Betancourt, M.R. and Thirumalai, D. (1999) Pair potentials for protein folding: choice of reference states and sensitivity of predicted native states to variations in the interaction schemes. Protein Sci8(2), 361–9.

    PubMed  CAS  Google Scholar 

  • Brusic, V., Petrovsky, N., et al. (2002) Prediction of promiscuous peptides that bind HLA class I molecules. Immunol Cell Biol80(3), 280–5.

    Article  PubMed  CAS  Google Scholar 

  • Brusic, V., Rudy, G., et al. (1998) Prediction of MHC class Il-binding peptides using an evolutionary algorithm and artificial neural network. Bioinformatics14(2), 121–30.

    Article  PubMed  CAS  Google Scholar 

  • Cochlovius, B., Stassar, M., et al. (2000) In vitro and in vivo induction of a Th cell response toward peptides of the melanoma-associated glycoprotein 100 protein selected by the TEPITOPE program. JImmunol165(8), 4731–41.

    CAS  Google Scholar 

  • Collins, E.J., Garboczi, D.N., et al. (1995) The three-dimensional structure of a class I major histocompatibility complex molecule missing the alpha 3 domain of the heavy chain. Proc NatlAcadSci USA92(4), 1218–21.

    Article  CAS  Google Scholar 

  • Cooper, S., Erickson, A.L., et al. (1999) Analysis of a successful immune response against hepatitis C virus. Immunity10(4), 439–49.

    Article  PubMed  CAS  Google Scholar 

  • D’Amaro, J., Houbiers, J.G., et al. (1995) A computer program for predicting possible cytotoxic T lymphocyte epitopes based on HLA class I peptide-binding motifs. Hum Immunol43(1), 13–8.

    Article  PubMed  CAS  Google Scholar 

  • Disis, M.L., Gralow, J.R., et al. (1996) Peptide-based, but not whole protein, vaccines elicit immunity to HER-2/neu, oncogenic self-protein. J Immunol156(9), 3151–8.

    PubMed  CAS  Google Scholar 

  • Donnes, P. and Elofsson, A. (2002) Prediction of MHC class I binding peptides, using SVMHC. BMC Bioinformatics3, 25.

    Article  PubMed  Google Scholar 

  • Doytchinova, LA., Blythe, M.J., et al. (2002) Additive method for the prediction of protein- peptide binding affinity. Application to the MHC class I molecule HLA-A*0201. J ProteomeRes1(3), 263–72.

    Article  CAS  Google Scholar 

  • Doytchinova, LA. and Flower, D.R. (2001) Toward the quantitative prediction of T-cell epitopes: coMFA and coMSIA studies of peptides with affinity for the class I MHC molecule HLA-A*0201. JMed Chem44(22), 3572–81.

    Article  CAS  Google Scholar 

  • Falk, K., Rotzschke, O., et al. (1990) Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature348(6298), 248–51.

    Article  PubMed  CAS  Google Scholar 

  • Free, S.M., Jr. and Wilson, J.W. (1964) A Mathematical Contribution To Structure-Activity Studies. JMed Chem53, 395–9.

    Article  Google Scholar 

  • Fremont, D.H., Stura, E.A., et al. (1995) Crystal structure of an H-2Kb-ovalbumin peptide complex reveals the interplay of primary and secondary anchor positions in the major histocompatibility complex binding groove. Proc Nail Acad Sci USA92(7),2479–83.

    Article  CAS  Google Scholar 

  • Gribskov, M., McLachlan, A.D., et al. (1987) Profile analysis: detection of distantly related proteins. Proc NatlAcadSci USA84(13), 4355–8.

    Article  CAS  Google Scholar 

  • Gross, D.M., Forsthuber, T., et al. (1998) Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis. Science281(5377), 703–6.

    Article  PubMed  CAS  Google Scholar 

  • Gulukota, K., Sidney, J., et al. (1997) Two complementary methods for predicting peptides binding major histocompatibility complex molecules. JMol Biol267(5), 1258–67.

    Article  CAS  Google Scholar 

  • Guo, H.C., Jardetzky, T.S., et al. (1992) Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle. Nature360(6402),364–6.

    Article  PubMed  CAS  Google Scholar 

  • Guo, H.C., Madden, D.R., et al. (1993) Comparison of the P2 specificity pocket in three human histocompatibility antigens: HLA-A*6801, HLA-A*0201, and HLA-B*2705. Proc NatlAcadSci USA90(17), 8053–7.

    Article  CAS  Google Scholar 

  • Hammer, J., Gallazzi, F., et al. (1995) Peptide binding specificity of HLA-DR4 molecules: correlation with rheumatoid arthritis association. JExp Med181(5), 1847–55.

    Article  CAS  Google Scholar 

  • Ishioka, G.Y., Fikes, J, et al. (1999) Utilization of MHC class I transgenic mice for development of minigene DNA vaccines encoding multiple HLA-restricted CTL epitopes. J Immunol162(7), 3915–25.

    PubMed  CAS  Google Scholar 

  • Iwasaki, A. and Barber, B.H. (1998) Induction by DNA immunization of a protective antitumor cytotoxic T lymphocyte response against a minimal-epitope-expressing tumor. Cancer Immunol Immunother45(5), 273–9.

    Article  PubMed  CAS  Google Scholar 

  • Jernigan, R.L. and Bahar, I. (1996) Structure-derived potentials and protein simulations. Curr Opin Struct Biol6(2), 195–209.

    Article  CAS  Google Scholar 

  • Jones, D.T. and Thornton, J.M. (1996) Potential energy functions for threading. Curr Opin Struct Biol6(2), 210–6.

    CAS  Google Scholar 

  • Kangueane, P. and Sakharkar, M.K. (2005) T-Epitope Designer: A HLA-peptide binding prediction server. Bioinformation1 (1), 21–24.

    PubMed  Google Scholar 

  • Kawashima, I., Hudson, S.J., et al. (1998) The multi-epitope approach for immunotherapy for cancer: identification of several CTL epitopes from various tumor-associated antigens expressed on solid epithelial tumors. Hum Immunol59(1), 1–14.

    Article  PubMed  CAS  Google Scholar 

  • Kubo, R.T., Sette, A., et al. (1994) Definition of specific peptide motifs for four major HLA- A alleles. J Immunol152(8), 3913–24.

    PubMed  CAS  Google Scholar 

  • Logean, A. and Rognan, D. (2002) Recovery of known T-cell epitopes by computational scanning of a viral genome. J Comput Aided Mol Des16(4), 229–43.

    Article  PubMed  CAS  Google Scholar 

  • Logean, A., Sette, A., et al. (2001) Customized versus universal scoring functions: application to class I MHC-peptide binding free energy predictions. Bioorg Med Chem Lett11(5), 675–9.

    Article  PubMed  CAS  Google Scholar 

  • Madden, D.R., Garboczi, D.N., et al. (1993) The antigenic identity of peptide-MHC complexes: a comparison of the conformations of five viral peptides presented by HLA- A2.Ce// 75(4), 693–708.

    CAS  Google Scholar 

  • Madden, D.R., Gorga, J.C., et al. (1992) The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC. Cell70(6), 1035–48.

    Article  PubMed  CAS  Google Scholar 

  • Mallios, R.R. (1999) Class II MHC quantitative binding motifs derived from a large molecular database with a versatile iterative stepwise discriminant analysis meta- algorithm. Bioinformatics15(6), 432–9.

    Article  PubMed  CAS  Google Scholar 

  • Mamitsuka, H. (1998) Predicting peptides that bind to MHC molecules using supervised learning of hidden Markov models. Proteins33(4), 460–74.

    Article  PubMed  CAS  Google Scholar 

  • Meister, G.E., Roberts, C.G., et al. (1995) Two novel T cell epitope prediction algorithms based on MHC-binding motifs; comparison of predicted and published epitopes from Mycobacterium tuberculosis and HTV protein sequences. Vaccine13(6), 581–91.

    Article  PubMed  CAS  Google Scholar 

  • Milik, M., Sauer, D., et al. (1998) Application of an artificial neural network to predict specific class I MHC binding peptide sequences. Nat Biotechnol16(8), 753–6.

    Article  PubMed  CAS  Google Scholar 

  • Miyazawa, S. and Jernigan, R.L. (1985) Estimation of effective inter-residue contact energies from protein crystal structure, quasi-chemical approximation. Macromolecules18, 534.

    Article  CAS  Google Scholar 

  • Miyazawa, S. and Jernigan, R.L. (1996) Residue-residue potentials with a favorable contact pair term and an unfavorable high packing density term, for simulation and threading. J Mol Biol256(3), 623–44.

    Article  PubMed  CAS  Google Scholar 

  • Morgan, D.J., Kreuwel, H.T., et al. (1998) Activation of low avidity CTL specific for a self epitope results in tumor rejection but not autoimmunity. JImmunol160(2), 643–51.

    CAS  Google Scholar 

  • Noguchi, H., Kato, R., et al. (2002) Hidden Markov model-based prediction of antigenic peptides that interact with MHC class II molecules. JBiosci Bioeng94(3), 264–70.

    Article  CAS  Google Scholar 

  • Pamer, E. and Cresswell, P. (1998) Mechanisms of MHC class I—restricted antigen processing. Annu Rev Immunol16, 323–58.

    Article  PubMed  CAS  Google Scholar 

  • Parker, K.C., Bednarek, M.A., et al. (1994) Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol 152(1), 163–75.

    PubMed  CAS  Google Scholar 

  • Rammensee, H., Bachmann, I, et al. (1999) SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics50(3-4), 213–9.

    Article  PubMed  CAS  Google Scholar 

  • Rammensee, H.G., Friede, T., et al. (1995) MHC ligands and peptide motifs: first listing. Immunogenetics41(4), 178–228.

    Article  PubMed  CAS  Google Scholar 

  • Reche, P.A., Glutting, IP., et al. (2002) Prediction of MHC class I binding peptides using profile motifs. Hum Immunol63(9), 701–9.

    Article  PubMed  CAS  Google Scholar 

  • Robinson, I, Waller, M.J., et al. (2003) IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex. Nucleic Acids Res31(1), 311–4.

    Article  PubMed  CAS  Google Scholar 

  • Rognan, D., Lauemoller, S.L., et al. (1999) Predicting binding affinities of protein ligands from three-dimensional models: application to peptide binding to class I major histocompatibility proteins. JMed Chem42(22), 4650–8.

    Article  CAS  Google Scholar 

  • Rognan, D., Scapozza, L., et al. (1994) Molecular dynamics simulation of MHC-peptide complexes as a tool for predicting potential T cell epitopes. Biochemistry33(38), 11476–85.

    Article  PubMed  CAS  Google Scholar 

  • Ruppert, J., Sidney, J., et al. (1993) Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell74(5), 929–37.

    Article  PubMed  CAS  Google Scholar 

  • Saper, M.A., Bjorkman, P.J., et al. (1991) Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution. J Mol Biol219(2), 277–319.

    Article  PubMed  CAS  Google Scholar 

  • Sarobe, P., Pendleton, CD., et al. (1998) Enhanced in vitro potency and in vivo immunogenicity of a CTL epitope from hepatitis C virus core protein following amino acid replacement at secondary HLA-A2.1 binding positions. J Clin Invest102(6), 1239–48.

    Article  PubMed  CAS  Google Scholar 

  • Schueler-Furman, O., Altuvia, Y., et al. (2000) Structure-based prediction of binding peptides to MHC class I molecules: application to a broad range of MHC alleles. Protein Sci9(9), 1838–46.

    Article  PubMed  CAS  Google Scholar 

  • Schueler-Furman, O., Elber, R, et al. (1998) Knowledge-based structure prediction of MHC class I bound peptides: a study of 23 complexes. Fold Des3(6), 549–64.

    Article  PubMed  CAS  Google Scholar 

  • Sette, A., Buus, S., et al. (1989) Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis. Proc NatlAcadSci USA86(9), 3296–300.

    Article  CAS  Google Scholar 

  • Sette, A., Vitiello, A., et al. (1994) The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J Immunol153(12), 5586–92.

    PubMed  CAS  Google Scholar 

  • Skolnick, J., Jaroszewski, L., et al. (1997) Derivation and testing of pair potentials for protein folding. When is the quasichemical approximation correct? Protein Sci6(3), 676–88.

    Article  PubMed  CAS  Google Scholar 

  • Stassar, M.J., Raddrizzani, L., et al. (2001) T-helper cell-response to MHC class H-binding peptides of the renal cell carcinoma-associated antigen RAGE-1. Immunobiology203(5), 743–55.

    PubMed  CAS  Google Scholar 

  • Stryhn, A., Pedersen, L.O., et al. (1996) Peptide binding specificity of major histocompatibility complex class I resolved into an array of apparently independent subspecificities: quantitation by peptide libraries and improved prediction of binding. Eur J Immunol26(8), 1911–8.

    Article  PubMed  CAS  Google Scholar 

  • Sturniolo, T., Bono, E., et al. (1999) Generation of tissue-specific and promiscuous HLA ligand databases using DNA microarrays and virtual HLA class II matrices. Nat Biotechnol17(6), 555–61.

    Article  PubMed  CAS  Google Scholar 

  • Thompson, J.D., Higgins, D.G., et al. (1994) Improved sensitivity of profile searches through the use of sequence weights and gap excision. Comput Appl Biosci10(1), 19–29.

    PubMed  CAS  Google Scholar 

  • Townsend, A.R., Rothbard, J., et al. (2006) The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. 1986. J Immunol176(9), 5141–50.

    PubMed  CAS  Google Scholar 

  • Udaka, K., Wiesmuller, K.H., et al. (2000) An automated prediction of MHC class I-binding peptides based on positional scanning with peptide libraries. Immunogenetics51(10), 816–28.

    Article  PubMed  CAS  Google Scholar 

  • van der Burg, S.H., Visseren, M.J., et al. (1996) Immunogenicity of peptides bound to MHC class I molecules depends on the MHC-peptide complex stability. J Immunol156(9), 3308–14.

    PubMed  Google Scholar 

  • Viret, C. and Janeway, C.A., Jr. (1999) MHC and T cell development. Rev Immunogenet1(1), 91–104.

    PubMed  CAS  Google Scholar 

  • Zeng, J., Treutlein, H.R., et al. (2001) Predicting sequences and structures of MHC-binding peptides: a computational combinatorial approach. J Comput Aided Mol Des15, 573.

    Article  CAS  Google Scholar 

  • Zhao, B., Mathura, V.S., et al. (2003) A novel MHCp binding prediction model. Hum Immunol64(12), 1123?–43.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Kangueane, P., Zhao, B., Sakharkar, M.K. (2009). Computational Immunology: HLA-peptide Binding Prediction. In: Mathura, V.S., Kangueane, P. (eds) Bioinformatics: A Concept-Based Introduction. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-84870-9_11

Download citation

Publish with us

Policies and ethics