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

Nicolas Rapin¹, Ilka Hoof^2,3, Ole Lund², Morten Nielsen²

¹Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark
²Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark
³Department of Theoretical Biology/Bioinformatics, Utrecht University, Utrecht, The Netherlands

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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Introduction
Methods
Applications
Summary
Acknowledgements
Literature Cited
Figures
Tables

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Figures

Figure 18.17.1

Left: Kullback-Leibler (KL) sequence logo for the HLA-A*0201 allele. The KL information content is plotted along the 9-mer peptide sequence (solid blue line). Amino acids with positive influence on the binding are plotted on the positive y axis, and amino acids with a negative influence on binding are plotted on the negative y axis. The relative height of each amino acid is given by Equation 18.17.7, in the text. Right: The contact map for the HLA-A*0201 allele visualizes which residues of the MHC pseudosequence are in contact with which positions in the 9-mer peptide.

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Figure 18.17.2

Home screen for the MHC Motif Viewer Web site. The different pictures are clickable and take the user to different sections of the Web site for the six animal species (human, pig, mouse, gorilla, chimpanzee, and macaque) for which MHC binding motifs were computed. On top of the screen, a quick menu bar allows the user to navigate to the Help and MHC Fight sections.

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Figure 18.17.3

Species/loci overview. The alleles are arranged on a grid and are clickable. Comparison is made easy because the user has a simultaneous overview of many alleles.

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Figure 18.17.4

Detailed view of the human HLA-A*0201 motif logo. The Logo link allows the user to download the motif image in jpg format (logo), the Matrix link allows the user to download the PSSM matrix in Blast profile format, and the Pseudo seq link directs the user to a graphical plot of the contact-matrix (see Fig. 18.17.1). The pie-chart above the logo shows the estimated Pearson correlation coefficient for the NetMHCpan predictions for the given allele. This value is shown together with the closest neighbor and the distance to this neighboring allele.

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Figure 18.17.5

Motif logos of (A) HLA-A*3001 and HLA-A*3002 and (B) HLA-A*6801 and HLA-A*6901. Both panels show examples of allele pairs that show a high similarity on a protein-sequence level while revealing clear differences in the C-terminal amino acid preference. Logos were displayed using the MHC Fight Viewer.

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Figure 18.17.6

Motif logos of HLA-A*0201, A*0301, A*0265, and A*0280. The logos reveal the similarity in binding specificity between A*0301 and A*0265, which is unexpected given the serotype of these molecules. A*0280 shares the A2 supertype binding preference, exemplified by A*0201. Logos were displayed using the MHC Fight Viewer.

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Figure 18.17.7

Motif logos of the Patr-A*0701, HLA-A*2402, Patr-B*1301, and HLA-B*0702. The motif logos illustrate the shared binding specificity that can be observed for some chimpanzee and human MHC class I molecules. Logos were displayed using the MHC Fight Viewer.

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Figure 18.17.8

Motif logos of the pig MHC class I allele SLA-2*0601 and the human allele HLA-B*4001. The logos illustrate their shared binding specificity. Logos were displayed using the MHC Fight Viewer.

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Figure 18.17.9

Motif logos representing a patient's HLA genotype.

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