Table of Contents Author Guidelines Submit a Manuscript
Journal of Immunology Research
Volume 2017 (2017), Article ID 9363750, 15 pages
https://doi.org/10.1155/2017/9363750
Research Article

Computer-Aided Design of an Epitope-Based Vaccine against Epstein-Barr Virus

1Barcelona Institute for Global Health (ISGlobal), Centre for Research in International Health (CRESIB), Hospital Clinic-University of Barcelona, Barcelona, Spain
2Laboratory of Immunomedicine, Faculty of Medicine, University Complutense of Madrid, Ave Complutense S/N, 28040 Madrid, Spain

Correspondence should be addressed to Pedro A. Reche

Received 19 May 2017; Revised 7 August 2017; Accepted 20 August 2017; Published 28 September 2017

Academic Editor: Peirong Jiao

Copyright © 2017 Julio Alonso-Padilla et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Z. Lin, X. Wang, M. J. Strong et al., “Whole-genome sequencing of the Akata and Mutu Epstein-Barr virus strains,” Journal of Virology, vol. 87, no. 2, pp. 1172–1182, 2013. View at Publisher · View at Google Scholar · View at Scopus
  2. K. Sathiyamoorthy, J. Jiang, Y. X. Hu et al., “Assembly and architecture of the EBV B cell entry triggering complex,” PLoS Pathogens, vol. 10, no. 8, article e1004309, 2014. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Neves, J. Marinho-Dias, J. Ribeiro, and H. Sousa, “Epstein-Barr virus strains and variations: geographic or disease-specific variants?” Journal of Medical Virology, vol. 89, no. 3, pp. 373–387, 2017. View at Publisher · View at Google Scholar · View at Scopus
  4. L. S. Young and A. B. Rickinson, “Epstein-Barr virus: 40 years on,” Nature Reviews Cancer, vol. 4, no. 10, pp. 757–768, 2004. View at Publisher · View at Google Scholar · View at Scopus
  5. E. K. Vetsika and M. Callan, “Infectious mononucleosis and Epstein-Barr virus,” Expert Reviews in Molecular Medicine, vol. 6, no. 23, pp. 1–16, 2004. View at Publisher · View at Google Scholar · View at Scopus
  6. G. C. Faulkner, S. R. Burrows, R. Khanna, D. J. Moss, A. G. Bird, and D. H. Crawford, “X-linked agammaglobulinemia patients are not infected with Epstein-Barr virus: implications for the biology of the virus,” Journal of Virology, vol. 73, no. 2, pp. 1555–1564, 1999. View at Google Scholar
  7. C. D. Shannon-Lowe, B. Neuhierl, G. Baldwin, A. B. Rickinson, and H. J. Delecluse, “Resting B cells as a transfer vehicle for Epstein-Barr virus infection of epithelial cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 18, pp. 7065–7070, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. B. Kempkes and E. S. Robertson, “Epstein-Barr virus latency: current and future perspectives,” Current Opinion in Virology, vol. 14, pp. 138–144, 2015. View at Publisher · View at Google Scholar · View at Scopus
  9. M. M. Mullen, K. M. Haan, R. Longnecker, and T. S. Jardetzky, “Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II receptor HLA-DR1,” Molecular Cell, vol. 9, no. 2, pp. 375–385, 2002. View at Publisher · View at Google Scholar · View at Scopus
  10. G. S. Taylor, H. M. Long, J. M. Brooks, A. B. Rickinson, and A. D. Hislop, “The immunology of Epstein-Barr virus-induced disease,” Annual Review of Immunology, vol. 33, pp. 787–821, 2015. View at Publisher · View at Google Scholar · View at Scopus
  11. D. A. Thorley-Lawson, “Epstein-Barr virus: exploiting the immune system,” Nature Reviews Immunology, vol. 1, no. 1, pp. 75–82, 2001. View at Publisher · View at Google Scholar
  12. T. Strowig, F. Brilot, F. Arrey et al., “Tonsilar NK cells restrict B cell transformation by the Epstein-Barr virus via IFN-gamma,” PLoS Pathogens, vol. 4, no. 2, article e27, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. A. D. Hislop, G. S. Taylor, D. Sauce, and A. B. Rickinson, “Cellular responses to viral infection in humans: lessons from Epstein-Barr virus,” Annual Review of Immunology, vol. 25, pp. 587–617, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. J. M. Brooks, H. M. Long, R. J. Tierney et al., “Early T cell recognition of B cells following Epstein-Barr virus infection: identifying potential targets for prophylactic vaccination,” PLoS Pathogens, vol. 12, no. 4, article e1005549, 2016. View at Publisher · View at Google Scholar · View at Scopus
  15. E. Amyes, C. Hatton, D. Montamat-Sicotte et al., “Characterization of the CD4+ T cell response to Epstein-Barr virus during primary and persistent infection,” The Journal of Experimental Medicine, vol. 198, no. 6, pp. 903–911, 2003. View at Publisher · View at Google Scholar · View at Scopus
  16. W. Bu, G. M. Hayes, H. Liu et al., “Kinetics of Epstein-Barr virus (EBV) neutralizing and virus-specific antibodies after primary infection with EBV,” Clinical and Vaccine Immunology, vol. 23, no. 4, pp. 363–369, 2016. View at Publisher · View at Google Scholar · View at Scopus
  17. M. De Paschale and P. Clerici, “Serological diagnosis of Epstein-Barr virus infection: problems and solutions,” World Journal of Virology, vol. 1, no. 1, pp. 31–43, 2012. View at Publisher · View at Google Scholar
  18. M. P. Thompson and R. Kurzrock, “Epstein-Barr virus and cancer,” Clinical Cancer Research, vol. 10, no. 3, pp. 803–821, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. A. Ascherio and K. L. Munger, “EBV and autoimmunity,” Current Topics in Microbiology and Immunology, vol. 390, Part 1, pp. 365–385, 2015. View at Publisher · View at Google Scholar · View at Scopus
  20. J. I. Cohen, “Epstein-Barr virus vaccines,” Clinical & Translational Immunology, vol. 4, no. 1, article e32, 2015. View at Publisher · View at Google Scholar
  21. P. A. Reche, D. B. Keskin, R. E. Hussey, P. Ancuta, D. Gabuzda, and E. L. Reinherz, “Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes,” Medical Immunology, vol. 5, p. 1, 2006. View at Publisher · View at Google Scholar · View at Scopus
  22. Q. M. Sheikh, D. Gatherer, P. A. Reche, and D. R. Flower, “Towards the knowledge-based design of universal influenza epitope ensemble vaccines,” Bioinformatics, vol. 32, no. 21, pp. 3233–3239, 2016. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Molero-Abraham, J. P. Glutting, D. R. Flower, E. M. Lafuente, and P. A. Reche, “EPIPOX: immunoinformatic characterization of the shared T-cell epitome between variola virus and related pathogenic Orthopoxviruses,” Journal of Immunology Research, vol. 2015, Article ID 738020, 11 pages, 2015. View at Publisher · View at Google Scholar · View at Scopus
  24. C. M. Diez-Rivero and P. A. Reche, “CD8 T cell epitope distribution in viruses reveals patterns of protein biosynthesis,” PLoS One, vol. 7, no. 8, article e43674, 2012. View at Publisher · View at Google Scholar · View at Scopus
  25. P. A. Reche, H. Zhang, J. P. Glutting, and E. L. Reinherz, “EPIMHC: a curated database of MHC-binding peptides for customized computational vaccinology,” Bioinformatics, vol. 21, no. 9, pp. 2140-2141, 2005. View at Publisher · View at Google Scholar · View at Scopus
  26. Q. Zhang, P. Wang, Y. Kim et al., “Immune epitope database analysis resource (IEDB-AR),” Nucleic Acids Research, vol. 36, Web Server issue, pp. W513–W518, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. W. Li and A. Godzik, “Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences,” Bioinformatics, vol. 22, no. 13, pp. 1658-1659, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Federhen, “Type material in the NCBI taxonomy database,” Nucleic Acids Research, vol. 43, Database issue, pp. D1086–D1098, 2015. View at Publisher · View at Google Scholar · View at Scopus
  29. R. C. Edgar, “MUSCLE: multiple sequence alignment with high accuracy and high throughput,” Nucleic Acids Research, vol. 32, no. 5, pp. 1792–1797, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. C. E. Shannon, “The mathematical theory of communication,” The Bell System Technical Journal, vol. 27, pp. 379–423, 1948, 623-656. View at Google Scholar
  31. M. Garcia-Boronat, C. M. Diez-Rivero, E. L. Reinherz, and P. A. Reche, “PVS: a web server for protein sequence variability analysis tuned to facilitate conserved epitope discovery,” Nucleic Acids Research, vol. 36, Web Server issue, pp. W35–W41, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. P. A. Reche and E. L. Reinherz, “Sequence variability analysis of human class I and class II MHC molecules: functional and structural correlates of amino acid polymorphisms,” Journal of Molecular Biology, vol. 331, no. 3, pp. 623–641, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. J. J. Stewart, C. Y. Lee, S. Ibrahim et al., “A Shannon entropy analysis of immunoglobulin and T cell receptor,” Molecular Immunology, vol. 34, pp. 1067–1082, 1997. View at Publisher · View at Google Scholar · View at Scopus
  34. P. A. Reche, J.-P. Glutting, and E. L. Reinherz, “Enhancement to the RANKPEP resource for the prediction of peptide binding to MHC molecules using profiles,” Immunogenetics, vol. 56, pp. 405–419, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. P. A. Reche, J. P. Glutting, and E. L. Reinherz, “Prediction of MHC class I binding peptides using profile motifs,” Human Immunology, vol. 63, no. 9, pp. 701–709, 2002. View at Publisher · View at Google Scholar · View at Scopus
  36. P. A. Reche and E. L. Reinherz, “Prediction of peptide-MHC binding using profiles,” Methods in Molecular Biology, vol. 409, pp. 185–200, 2007. View at Publisher · View at Google Scholar
  37. J. Greenbaum, J. Sidney, J. Chung, C. Brander, B. Peters, and A. Sette, “Functional classification of class II human leukocyte antigen (HLA) molecules reveals seven different supertypes and a surprising degree of repertoire sharing across supertypes,” Immunogenetics, vol. 63, no. 6, pp. 325–335, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. P. Wang, J. Sidney, Y. Kim et al., “Peptide binding predictions for HLA DR, DP and DQ molecules,” BMC Bioinformatics, vol. 11, p. 568, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. M. Molero-Abraham, E. M. Lafuente, D. R. Flower, and P. A. Reche, “Selection of conserved epitopes from hepatitis C virus for pan-populational stimulation of T-cell responses,” Clinical & Developmental Immunology, vol. 2013, Article ID 601943, 10 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  40. K. Cao, J. Hollenbach, X. Shi, W. Shi, M. Chopek, and M. A. Fernandez-Vina, “Analysis of the frequencies of HLA-A, B, and C alleles and haplotypes in the five major ethnic groups of the United States reveals high levels of diversity in these loci and contrasting distribution patterns in these populations,” Human Immunology, vol. 62, no. 9, pp. 1009–1030, 2001. View at Publisher · View at Google Scholar · View at Scopus
  41. H. H. Bui, J. Sidney, K. Dinh, S. Southwood, M. J. Newman, and A. Sette, “Predicting population coverage of T-cell epitope-based diagnostics and vaccines,” BMC Bioinformatics, vol. 7, p. 153, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. S. J. Hubbard and J. M. Thornton, NACCESS, Computer Program, Department of Biochemistry and Molecular Biology, University College London, London, England, UK, 1993.
  43. M. Magrane, “UniProt Knowledgebase: a hub of integrated protein data,” Database: The Journal of Biological Databases and Curation, vol. 2011, article bar009, 2011. View at Publisher · View at Google Scholar · View at Scopus
  44. S. F. Altschul, T. L. Madden, A. A. Schaffer et al., “Gapped BLAST and PSI-BLAST: a new generation of protein database search programs,” Nucleic Acids Research, vol. 25, no. 17, pp. 3389–3402, 1997. View at Google Scholar
  45. J. Peterson, S. Garges, M. Giovanni et al., “The NIH Human Microbiome Project,” Genome Research, vol. 19, no. 12, pp. 2317–2323, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. L. H. Glimcher and C. J. Kara, “Sequences and factors: a guide to MHC class-II transcription,” Annual Review of Immunology, vol. 10, pp. 13–49, 1992. View at Publisher · View at Google Scholar
  47. L. J. Stern and J. M. Calvo-Calle, “HLA-DR: molecular insights and vaccine design,” Current Pharmaceutical Design, vol. 15, no. 28, pp. 3249–3261, 2009. View at Google Scholar
  48. G. Szakonyi, M. G. Klein, J. P. Hannan et al., “Structure of the Epstein-Barr virus major envelope glycoprotein,” Nature Structural & Molecular Biology, vol. 13, no. 11, pp. 996–1001, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Backovic, R. Longnecker, and T. S. Jardetzky, “Structure of a trimeric variant of the Epstein-Barr virus glycoprotein B,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 8, pp. 2880–2885, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. E. Westhof, D. Altschuh, D. Moras et al., “Correlation between segmental mobility and the location of antigenic determinants in proteins,” Nature, vol. 311, no. 5982, pp. 123–126, 1984. View at Publisher · View at Google Scholar · View at Scopus
  51. A. N. Kirschner, J. Sorem, R. Longnecker, and T. S. Jardetzky, “Structure of Epstein-Barr virus glycoprotein 42 suggests a mechanism for triggering receptor-activated virus entry,” Structure, vol. 17, no. 2, pp. 223–233, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. K. Sathiyamoorthy, Y. X. Hu, B. S. Mohl, J. Chen, R. Longnecker, and T. S. Jardetzky, “Structural basis for Epstein-Barr virus host cell tropism mediated by gp42 and gHgL entry glycoproteins,” Nature Communications, vol. 7, article 13557, 2016. View at Publisher · View at Google Scholar · View at Scopus
  53. C. Smith and R. Khanna, “The development of prophylactic and therapeutic EBV vaccines,” Current Topics in Microbiology and Immunology, vol. 391, pp. 455–473, 2015. View at Publisher · View at Google Scholar · View at Scopus
  54. H. H. Balfour Jr., “Progress, prospects, and problems in Epstein-Barr virus vaccine development,” Current Opinion in Virology, vol. 6, pp. 1–5, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. E. M. Sokal, K. Hoppenbrouwers, C. Vandermeulen et al., “Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults,” The Journal of Infectious Diseases, vol. 196, no. 12, pp. 1749–1753, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. R. Lin, D. Heeke, H. Liu et al., “Development of a robust, higher throughput green fluorescent protein (GFP)-based Epstein-Barr virus (EBV) micro-neutralization assay,” Journal of Virological Methods, vol. 247, pp. 15–21, 2017. View at Publisher · View at Google Scholar
  57. S. L. Elliott, A. Suhrbier, J. J. Miles et al., “Phase I trial of a CD8+ T-cell peptide epitope-based vaccine for infectious mononucleosis,” Journal of Virology, vol. 82, no. 3, pp. 1448–1457, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. L. M. Hutt-Fletcher, “EBV glycoproteins: where are we now?” Future Virology, vol. 10, no. 10, pp. 1155–1162, 2015. View at Publisher · View at Google Scholar · View at Scopus
  59. V. Dasari, K. H. Bhatt, C. Smith, and R. Khanna, “Designing an effective vaccine to prevent Epstein-Barr virus-associated diseases: challenges and opportunities,” Expert Review of Vaccines, vol. 16, no. 4, pp. 377–390, 2017. View at Publisher · View at Google Scholar
  60. J. Ponomarenko and M. Van Regenmortel, “B-cell epitope prediction,” in Structural Bioinformatics, pp. 849–879, John Wiley & Sons, Hoboken, NJ, USA, 2009. View at Google Scholar
  61. M. H. Van Regenmortel, “What is a B-cell epitope?” Methods in Molecular Biology, vol. 524, pp. 3–20, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. P. A. Reche and E. L. Reinherz, “Definition of MHC supertypes through clustering of MHC peptide-binding repertoires,” Methods in Molecular Biology, vol. 409, pp. 163–173, 2007. View at Publisher · View at Google Scholar
  63. P. Sun, H. Ju, Z. Liu et al., “Bioinformatics resources and tools for conformational B-cell epitope prediction,” Computational and Mathematical Methods in Medicine, vol. 2013, Article ID 943636, 11 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  64. L. Potocnakova, M. Bhide, and L. B. Pulzova, “An introduction to B-cell epitope mapping and in silico epitope prediction,” Journal of Immunology Research, vol. 2016, Article ID 6760830, 11 pages, 2016. View at Publisher · View at Google Scholar
  65. M. J. Blythe and D. R. Flower, “Benchmarking B cell epitope prediction: underperformance of existing methods,” Protein Science, vol. 14, no. 1, pp. 246–248, 2005. View at Publisher · View at Google Scholar · View at Scopus
  66. J. Gao and L. Kurgan, “Computational prediction of B cell epitopes from antigen sequences,” Methods in Molecular Biology, vol. 1184, pp. 197–215, 2014. View at Publisher · View at Google Scholar · View at Scopus
  67. K. A. Young, A. P. Herbert, P. N. Barlow, V. M. Holers, and J. P. Hannan, “Molecular basis of the interaction between complement receptor type 2 (CR2/CD21) and Epstein-Barr virus glycoprotein gp350,” Journal of Virology, vol. 82, no. 22, pp. 11217–11227, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. J. E. Tanner, M. Coincon, V. Leblond et al., “Peptides designed to spatially depict the Epstein-Barr virus major virion glycoprotein gp350 neutralization epitope elicit antibodies that block virus-neutralizing antibody 72A1 interaction with the native gp350 molecule,” Journal of Virology, vol. 89, no. 9, pp. 4932–4941, 2015. View at Publisher · View at Google Scholar · View at Scopus
  69. V. Litwin, J. Gumperz, P. Parham, J. H. Phillips, and L. L. Lanier, “Specificity of HLA class I antigen recognition by human NK clones: evidence for clonal heterogeneity, protection by self and non-self alleles, and influence of the target cell type,” The Journal of Experimental Medicine, vol. 178, no. 4, pp. 1321–1336, 1993. View at Google Scholar
  70. R. Arnon and T. Ben-Yedidia, “Old and new vaccine approaches,” International Immunopharmacology, vol. 3, no. 8, pp. 1195–1204, 2003. View at Publisher · View at Google Scholar · View at Scopus
  71. J. L. Whitton, N. Sheng, M. B. Oldstone, and T. A. McKee, “A “string-of-beads” vaccine, comprising linked minigenes, confers protection from lethal-dose virus challenge,” Journal of Virology, vol. 67, no. 1, pp. 348–352, 1993. View at Google Scholar
  72. S. Gupta, P. Kapoor, K. Chaudhary, A. Gautam, R. Kumar, and G. P. Raghava, “In silico approach for predicting toxicity of peptides and proteins,” PLoS One, vol. 8, no. 9, article e73957, 2013. View at Publisher · View at Google Scholar · View at Scopus
  73. E. M. Varypataki, N. Benne, J. Bouwstra, W. Jiskoot, and F. Ossendorp, “Efficient eradication of established tumors in mice with cationic liposome-based synthetic long-peptide vaccines,” Cancer Immunology Research, vol. 5, no. 3, pp. 222–233, 2017. View at Publisher · View at Google Scholar
  74. R. Kuai, L. J. Ochyl, K. S. Bahjat, A. Schwendeman, and J. J. Moon, “Designer vaccine nanodiscs for personalized cancer immunotherapy,” Nature Materials, vol. 16, no. 4, pp. 489–496, 2017. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Brazzoli, D. Magini, A. Bonci et al., “Induction of broad-based immunity and protective efficacy by self-amplifying mRNA vaccines encoding influenza virus hemagglutinin,” Journal of Virology, vol. 90, no. 1, pp. 332–344, 2015. View at Publisher · View at Google Scholar · View at Scopus
  76. R. A. Schwendener, “Liposomes as vaccine delivery systems: a review of the recent advances,” Therapeutic Advances in Vaccines, vol. 2, no. 6, pp. 159–182, 2014. View at Publisher · View at Google Scholar
  77. D. Felnerova, J. F. Viret, R. Gluck, and C. Moser, “Liposomes and virosomes as delivery systems for antigens, nucleic acids and drugs,” Current Opinion in Biotechnology, vol. 15, no. 6, pp. 518–529, 2004. View at Publisher · View at Google Scholar · View at Scopus
  78. Y. Perrie, D. Kirby, V. W. Bramwell, and A. R. Mohammed, “Recent developments in particulate-based vaccines,” Recent Patents on Drug Delivery & Formulation, vol. 1, no. 2, pp. 117–129, 2007. View at Publisher · View at Google Scholar
  79. C. Gujer, B. Chatterjee, V. Landtwing, A. Raykova, D. McHugh, and C. Munz, “Animal models of Epstein Barr virus infection,” Current Opinion in Virology, vol. 13, pp. 6–10, 2015. View at Publisher · View at Google Scholar · View at Scopus
  80. C. Calcagno, R. Puzone, Y. E. Pearson et al., “Computer simulations of heterologous immunity: highlights of an interdisciplinary cooperation,” Autoimmunity, vol. 44, no. 4, pp. 304–314, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. “Proceedings of the IARC working group on the evaluation of carcinogenic risks to humans. Epstein-Barr virus and Kaposi’s sarcoma herpesvirus/human herpesvirus 8. Lyon, France, 17-24 June 1997,” IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 70, pp. 1–492, 1997.
  82. A. W. Lee, W. Foo, O. Mang et al., “Changing epidemiology of nasopharyngeal carcinoma in Hong Kong over a 20-year period (1980-99): an encouraging reduction in both incidence and mortality,” International Journal of Cancer, vol. 103, no. 5, pp. 680–685, 2003. View at Publisher · View at Google Scholar · View at Scopus
  83. W. Zhong, P. A. Reche, C. C. Lai, B. Reinhold, and E. L. Reinherz, “Genome-wide characterization of a viral cytotoxic T lymphocyte epitope repertoire,” The Journal of Biological Chemistry, vol. 278, no. 46, pp. 45135–45144, 2003. View at Publisher · View at Google Scholar · View at Scopus
  84. E. M. Lafuente and P. A. Reche, “Prediction of MHC-peptide binding: a systematic and comprehensive overview,” Current Pharmaceutical Design, vol. 15, no. 28, pp. 3209–3220, 2009. View at Publisher · View at Google Scholar · View at Scopus