The MHC Motif Viewer: A Visualization Tool for MHC Binding Motifs

Nicolas Rapin1, Ilka Hoof2, Ole Lund2, Morten Nielsen2

1 Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark, 2 Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark
Publication Name:  Current Protocols in Immunology
Unit Number:  Unit 18.17
DOI:  10.1002/0471142735.im1817s88
Online Posting Date:  February, 2010
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Abstract

In vertebrates, the onset of cellular immune reactions is controlled by presentation of peptides in complex with major histocompatibility complex (MHC) molecules to T cell receptors. In humans, MHCs are called human leukocyte antigens (HLAs). Different MHC molecules present different subsets of peptides, and knowledge of their binding specificities is important for understanding differences in the immune response between individuals. Algorithms predicting which peptides bind a given MHC molecule have recently been developed with high prediction accuracy. The utility of these algorithms is hampered by the lack of tools for browsing and comparing specificity of these molecules. We have developed a Web server, MHC Motif Viewer, which allows the display of the binding motif for MHC class I proteins for human, chimpanzee, rhesus monkey, mouse, and swine, as well as HLA‐DR protein sequences. The binding motif for each MHC molecule is predicted using state‐of‐the‐art, pan‐specific peptide‐MHC binding‐prediction methods, and is visualized as a sequence logo, in a format that allows for a comprehensive interpretation of binding motif anchor positions and amino acid preferences. Curr. Protoc. Immunol. 88:18.17.1‐18.17.13. © 2010 by John Wiley & Sons, Inc.

Keywords: MHC; HLA; T cell epitope; binding motif; binding specificity; viewer

     
 
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Table of Contents

  • Introduction
  • Methods
  • Applications
  • Summary
  • Acknowledgements
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

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Figures

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Literature Cited

Literature Cited
   Altschul, S.F., Madden, T.L., Schaffer, A.A., Zhang, J., Zhang, Z., Miller, W., and Lipman, D.J. 1997. Gapped BLAST and PSI‐BLAST: A new generation of protein database search programs. Nucleic Acids Res. 25:3389‐3402.
   Bui, H.H., Sidney, J., Peters, B., Sathiamurthy, M., Sinichi, A., Purton, K.A., Mothe, B.R., Chisari, F.V., Watkins, D.I., and Sette, A. 2005. Automated generation and evaluation of specific MHC binding predictive tools: ARB matrix applications. Immunogenetics 57:304‐314.
   Falk, K., Rotzschke, O., Stevanovic, S., Jung, G., and Rammensee, H.G. 1991. Allele‐specific motifs revealed by sequencing of self‐peptides eluted from MHC molecules. Nature 351:290‐296.
   Frahm, N., Yusim, K., Suscovich, T.J., Adams, S., Sidney, J., Hraber, P., Hewitt, H.S., Linde, C.H., Kavanagh, D.G., Woodberry, T., Henry, L.M., Faircloth, K., Listgarten, J., Kadie, C., Jojic, N., Sango, K., Brown, N.V., Pae, E., Zaman, M.T., Bihl, F., Khatri, A., John, M., Mallal, S., Marincola, F.M., Walker, B.D., Sette, A., Heckerman, D., Korber, B.T., and Brander, C. 2007. Extensive HLA class I allele promiscuity among viral CTL epitopes. Eur. J. Immunol. 37:2419‐2433.
   Henikoff, S. and Henikoff, J.G. 1992. Amino acid substitution matrices from protein blocks. Proc. Natl. Acad. Sci. U.S.A. 89:10915‐10919.
   Hillen, N., Mester, G., Lemmel, C., Weinzierl, A.O., Muller, M., Wernet, D., Hennenlotter, J., Stenzl, A., Rammensee, H.G., and Stevanovic, S. 2008. Essential differences in ligand presentation and T cell epitope recognition among HLA molecules of the HLA‐B44 supertype. Eur. J. Immunol. 38:2993‐3003.
   Hoof, I., Peters, B., Sidney, J., Pedersen, L.E., Sette, A., Lund, O., Buus, S., and Nielsen, M. 2008. NetMHCpan, a method for MHC class I binding prediction beyond humans. Immunogenetics. 61:1‐13.
   Jacob, L. and Vert, J.P. 2008. Efficient peptide‐MHC‐I binding prediction for alleles with few known binders. Bioinformatics 24:358‐366.
   Jojic, N., Reyes‐Gomez, M., Heckerman, D., Kadie, C., and Schueler‐Furman, O. 2006. Learning MHC I–peptide binding. Bioinformatics 22:E227‐E235.
   Kullback, S. and Leibler, R.A. 1951. On information and sufficiency. Ann. Inst. Stat. Math. 22:76‐86.
   Lin, H.H., Ray, S., Tongchusak, S., Reinherz, E.L., and Brusic, V. 2008a. Evaluation of MHC class I peptide binding prediction servers: Applications for vaccine research. BMC Immunol. 9:8.
   Lin, H.H., Zhang, G.L., Tongchusak, S., Reinherz, E.L., and Brusic, V. 2008b. Evaluation of MHC‐II peptide binding prediction servers: Applications for vaccine research. BMC Bioinformatics 9:S22.
   Lund, O., Nielsen, M., Kesmir, C., Petersen, A.G., Lundegaard, C., Worning, P., Sylvester‐Hvid, C., Lamberth, K., Roder, G., Justesen, S., Buus, S., and Brunak, S. 2004. Definition of supertypes for HLA molecules using clustering of specificity matrices. Immunogenetics 55:797‐810.
   Lundegaard, C., Lamberth, K., Harndahl, M., Buus, S., Lund, O., and Nielsen, M. 2008. NetMHC‐3.0: Accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8‐11. Nucleic Acids Res. 1:36
   Nielsen, M., Lundegaard, C., Worning, P., Lauemoller, S.L., Lamberth, K., Buus, S., Brunak, S., and Lund, O. 2003. Reliable prediction of T‐cell epitopes using neural networks with novel sequence representations. Protein Sci. 12:1007‐1017.
   Nielsen, M., Lundegaard, C., Worning, P., Hvid, C.S., Lamberth, K., Buus, S., Brunak, S., and Lund, O. 2004. Improved prediction of MHC class I and class II epitopes using a novel Gibbs sampling approach. Bioinformatics 20:1388‐1397.
   Nielsen, M., Lundegaard, C., Blicher, T., Lamberth, K., Harndahl, M., Justesen, S., Roder, G., Peters, B., Sette, A., Lund, O., and Buus, S. 2007. NetMHCpan, a method for quantitative predictions of peptide binding to any HLA‐A and ‐B locus protein of known sequence. PLoS ONE 2:E796.
   Nielsen, M., Lundegaard, C., Blicher, T., Peters, B., Sette, A., Justesen, S., Buus, S., and Lund, O. 2008. Quantitative predictions of peptide binding to any HLA‐DR molecule of known sequence: NetMHCIIpan. PLoS Comput. Biol. 4:E100107.
   Perez, C.L., Larsen, M.V., Gustafsson, R., Norstrom, M.M., Atlas, A., Nixon, D.F., Nielsen, M., Lund, O., and Karlsson, A.C. 2008. Broadly immunogenic HLA class I supertype‐restricted elite CTL epitopes recognized in a diverse population infected with different HIV‐1 subtypes. J. Immunol. 180:5092‐5100.
   Peters, B. and Sette, A. 2005. Generating quantitative models describing the sequence specificity of biological processes with the stabilized matrix method. BMC Bioinformatics 6:132.
   Rammensee, H., Bachmann, J., Emmerich, N.P., Bachor, O.A., and Stevanovic, S. 1999. SYFPEITHI: Database for MHC ligands and peptide motifs. Immunogenetics 50:213‐219.
   Rapin, N., Hoof, I., Lund, O., and Nielsen, M. 2008. MHC motif viewer. Immunogenetics 60:759‐765.
   Robinson, J., Waller, M.J., Parham, P., Bodmer, J.G., and Marsh, S.G.E. 2001. IMGT/HLA Database: A sequence database for the human major histocompatibility complex. Nucleic Acids Res. 29:210‐213.
   Schneider, T.D. and Stephens, R.M. 1990. Sequence logos: A new way to display consensus sequences. Nucleic Acids Res. 18:6097‐6100.
   Sette, A. and Sidney, J. 1999. Nine major HLA class I supertypes account for the vast preponderance of HLA‐A and –B polymorphism. Immunogenetics 50:201‐212.
   Sette, A., Fleri, W., Peters, B., Sathiamurthy, M., Bui, H.H., and Wilson, S. 2005. A roadmap for the immunomics of category A‐C pathogens. Immunity 22:155‐161.
   Shannon, C.E. 1948. A mathematical theory of communication. Bell Labs Tech. J. 27:379‐423; 623‐656.
   Sidney, J., Asabe, S., Peters, B., Purton, K.A., Chung, J., Pencille, T.J., Purcell, R., Walker, C.M., Chisari, F.V. and Sette, A. 2006. Detailed characterization of the peptide binding specificity of five common Patr class I MHC molecules. Immunogenetics 58:559‐570.
   Sidney, J., Peters, B., Frahm, N., Brander, C., and Sette, A. 2008. HLA class I supertypes: A revised and updated classification. BMC Immunol. 9:1.
   Thompson, C.B. 1995. New insights into V(D)J recombination and its role in the evolution of the immune system. Immunity 3:531‐539.
   UniProt. 2008. The universal protein resource (UniProt). Nucleic Acids Res. 36:D190‐D195.
   Yewdell, J.W. and Bennink, J.R. 1999. Immunodominance in major histocompatibility complex class I‐restricted T lymphocyte responses. Annu. Rev. Immunol. 17:51‐88.
   Yu, K., Petrovsky, N., Schonbach, C., Koh, J.Y., and Brusic, V. 2002. Methods for prediction of peptide binding to MHC molecules: A comparative study. Mol. Med. 8:137‐148.
   Zhang, H., Lundegaard, C., and Nielsen, M. 2009. Pan‐specific MHC class I predictors: A benchmark of HLA class I pan‐specific prediction methods. Bioinformatics 25:83‐89.
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