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. 2001 Jul-Aug;7(4):706–713. doi: 10.3201/eid0704.010419

Rapid determination of HLA B*07 ligands from the West Nile virus NY99 genome.

A S De Groot 1, C Saint-Aubin 1, A Bosma 1, H Sbai 1, J Rayner 1, W Martin 1
PMCID: PMC2631750  PMID: 11585536

Abstract

Defined T cell epitopes for West Nile (WN) virus may be useful for developing subunit vaccines against WN virus infection and diagnostic reagents to detect WN virus-specific immune response. We applied a bioinformatics (EpiMatrix) approach to search the WN virus NY99 genome for HLA B*07 restricted cytotoxic T cell (CTL) epitopes. Ninety-five of 3,433 WN virus peptides scored above a predetermined cutoff, suggesting that these would be likely to bind to HLA B*07 and would also be likely candidate CTL epitopes. Compared with other methods for genome mapping, derivation of these ligands was rapid and inexpensive. Major histocompatibility complex ligands identified by this method may be used to screen T cells from WN virus-exposed persons for cell-mediated response to WN virus or to develop diagnostic reagents for immunopathogenesis studies and epidemiologic surveillance.

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Selected References

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  1. Aihara H., Takasaki T., Matsutani T., Suzuki R., Kurane I. Establishment and characterization of Japanese encephalitis virus-specific, human CD4(+) T-cell clones: flavivirus cross-reactivity, protein recognition, and cytotoxic activity. J Virol. 1998 Oct;72(10):8032–8036. doi: 10.1128/jvi.72.10.8032-8036.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. doi: 10.1093/nar/25.17.3389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. An L. L., Whitton J. L. A multivalent minigene vaccine, containing B-cell, cytotoxic T-lymphocyte, and Th epitopes from several microbes, induces appropriate responses in vivo and confers protection against more than one pathogen. J Virol. 1997 Mar;71(3):2292–2302. doi: 10.1128/jvi.71.3.2292-2302.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Anderson J. F., Andreadis T. G., Vossbrinck C. R., Tirrell S., Wakem E. M., French R. A., Garmendia A. E., Van Kruiningen H. J. Isolation of West Nile virus from mosquitoes, crows, and a Cooper's hawk in Connecticut. Science. 1999 Dec 17;286(5448):2331–2333. doi: 10.1126/science.286.5448.2331. [DOI] [PubMed] [Google Scholar]
  5. Blattman J. N., Sourdive D. J., Murali-Krishna K., Ahmed R., Altman J. D. Evolution of the T cell repertoire during primary, memory, and recall responses to viral infection. J Immunol. 2000 Dec 1;165(11):6081–6090. doi: 10.4049/jimmunol.165.11.6081. [DOI] [PubMed] [Google Scholar]
  6. Callan M. F., Tan L., Annels N., Ogg G. S., Wilson J. D., O'Callaghan C. A., Steven N., McMichael A. J., Rickinson A. B. Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus In vivo. J Exp Med. 1998 May 4;187(9):1395–1402. doi: 10.1084/jem.187.9.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. De Groot A. S., Jesdale B. M., Szu E., Schafer J. R., Chicz R. M., Deocampo G. An interactive Web site providing major histocompatibility ligand predictions: application to HIV research. AIDS Res Hum Retroviruses. 1997 May 1;13(7):529–531. doi: 10.1089/aid.1997.13.529. [DOI] [PubMed] [Google Scholar]
  8. Goulder P. J., Phillips R. E., Colbert R. A., McAdam S., Ogg G., Nowak M. A., Giangrande P., Luzzi G., Morgan B., Edwards A. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med. 1997 Feb;3(2):212–217. doi: 10.1038/nm0297-212. [DOI] [PubMed] [Google Scholar]
  9. Hanke T., Schneider J., Gilbert S. C., Hill A. V., McMichael A. DNA multi-CTL epitope vaccines for HIV and Plasmodium falciparum: immunogenicity in mice. Vaccine. 1998 Feb;16(4):426–435. doi: 10.1016/s0264-410x(97)00296-x. [DOI] [PubMed] [Google Scholar]
  10. Jia X. Y., Briese T., Jordan I., Rambaut A., Chi H. C., Mackenzie J. S., Hall R. A., Scherret J., Lipkin W. I. Genetic analysis of West Nile New York 1999 encephalitis virus. Lancet. 1999 Dec 4;354(9194):1971–1972. doi: 10.1016/s0140-6736(99)05384-2. [DOI] [PubMed] [Google Scholar]
  11. Jin X., Roberts C. G., Nixon D. F., Safrit J. T., Zhang L. Q., Huang Y. X., Bhardwaj N., Jesdale B., DeGroot A. S., Koup R. A. Identification of subdominant cytotoxic T lymphocyte epitopes encoded by autologous HIV type 1 sequences, using dendritic cell stimulation and computer-driven algorithm. AIDS Res Hum Retroviruses. 2000 Jan 1;16(1):67–76. doi: 10.1089/088922200309610. [DOI] [PubMed] [Google Scholar]
  12. Johnston L. J., Halliday G. M., King N. J. Langerhans cells migrate to local lymph nodes following cutaneous infection with an arbovirus. J Invest Dermatol. 2000 Mar;114(3):560–568. doi: 10.1046/j.1523-1747.2000.00904.x. [DOI] [PubMed] [Google Scholar]
  13. Johnston L. J., Halliday G. M., King N. J. Phenotypic changes in Langerhans' cells after infection with arboviruses: a role in the immune response to epidermally acquired viral infection? J Virol. 1996 Jul;70(7):4761–4766. doi: 10.1128/jvi.70.7.4761-4766.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kurane I., Okamoto Y., Dai L. C., Zeng L. L., Brinton M. A., Ennis F. A. Flavivirus-cross-reactive, HLA-DR15-restricted epitope on NS3 recognized by human CD4+ CD8- cytotoxic T lymphocyte clones. J Gen Virol. 1995 Sep;76(Pt 9):2243–2249. doi: 10.1099/0022-1317-76-9-2243. [DOI] [PubMed] [Google Scholar]
  15. Lanciotti R. S., Roehrig J. T., Deubel V., Smith J., Parker M., Steele K., Crise B., Volpe K. E., Crabtree M. B., Scherret J. H. Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States. Science. 1999 Dec 17;286(5448):2333–2337. doi: 10.1126/science.286.5448.2333. [DOI] [PubMed] [Google Scholar]
  16. Ljunggren H. G., Stam N. J., Ohlén C., Neefjes J. J., Höglund P., Heemels M. T., Bastin J., Schumacher T. N., Townsend A., Kärre K. Empty MHC class I molecules come out in the cold. Nature. 1990 Aug 2;346(6283):476–480. doi: 10.1038/346476a0. [DOI] [PubMed] [Google Scholar]
  17. Lobigs M., Arthur C. E., Müllbacher A., Blanden R. V. The flavivirus nonstructural protein NS3 is a dominant source of cytotoxic T cell peptide determinants. Virology. 1994 Jul;202(1):195–201. doi: 10.1006/viro.1994.1335. [DOI] [PubMed] [Google Scholar]
  18. Murali-Krishna K., Altman J. D., Suresh M., Sourdive D. J., Zajac A. J., Miller J. D., Slansky J., Ahmed R. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity. 1998 Feb;8(2):177–187. doi: 10.1016/s1074-7613(00)80470-7. [DOI] [PubMed] [Google Scholar]
  19. Murali-Krishna K., Ravi V., Manjunath R. Cytotoxic T lymphocytes raised against Japanese encephalitis virus: effector cell phenotype, target specificity and in vitro virus clearance. J Gen Virol. 1994 Apr;75(Pt 4):799–807. doi: 10.1099/0022-1317-75-4-799. [DOI] [PubMed] [Google Scholar]
  20. Nardin E. H., Calvo-Calle J. M., Oliveira G. A., Nussenzweig R. S., Schneider M., Tiercy J. M., Loutan L., Hochstrasser D., Rose K. A totally synthetic polyoxime malaria vaccine containing Plasmodium falciparum B cell and universal T cell epitopes elicits immune responses in volunteers of diverse HLA types. J Immunol. 2001 Jan 1;166(1):481–489. doi: 10.4049/jimmunol.166.1.481. [DOI] [PubMed] [Google Scholar]
  21. Nijman H. W., Houbiers J. G., van der Burg S. H., Vierboom M. P., Kenemans P., Kast W. M., Melief C. J. Characterization of cytotoxic T lymphocyte epitopes of a self-protein, p53, and a non-self-protein, influenza matrix: relationship between major histocompatibility complex peptide binding affinity and immune responsiveness to peptides. J Immunother Emphasis Tumor Immunol. 1993 Aug;14(2):121–126. [PubMed] [Google Scholar]
  22. Okamoto Y., Kurane I., Leporati A. M., Ennis F. A. Definition of the region on NS3 which contains multiple epitopes recognized by dengue virus serotype-cross-reactive and flavivirus-cross-reactive, HLA-DPw2-restricted CD4+ T cell clones. J Gen Virol. 1998 Apr;79(Pt 4):697–704. doi: 10.1099/0022-1317-79-4-697. [DOI] [PubMed] [Google Scholar]
  23. Parker K. C., Bednarek M. A., Coligan J. E. Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol. 1994 Jan 1;152(1):163–175. [PubMed] [Google Scholar]
  24. Rammensee H., Bachmann J., Emmerich N. P., Bachor O. A., Stevanović S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics. 1999 Nov;50(3-4):213–219. doi: 10.1007/s002510050595. [DOI] [PubMed] [Google Scholar]
  25. Rappole J. H., Derrickson S. R., Hubálek Z. Migratory birds and spread of West Nile virus in the Western Hemisphere. Emerg Infect Dis. 2000 Jul-Aug;6(4):319–328. doi: 10.3201/eid0604.000401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schafer J. R., Jesdale B. M., George J. A., Kouttab N. M., De Groot A. S. Prediction of well-conserved HIV-1 ligands using a matrix-based algorithm, EpiMatrix. Vaccine. 1998 Nov;16(19):1880–1884. doi: 10.1016/s0264-410x(98)00173-x. [DOI] [PubMed] [Google Scholar]
  27. Shen J., T-To S. S., Schrieber L., King N. J. Early E-selectin, VCAM-1, ICAM-1, and late major histocompatibility complex antigen induction on human endothelial cells by flavivirus and comodulation of adhesion molecule expression by immune cytokines. J Virol. 1997 Dec;71(12):9323–9332. doi: 10.1128/jvi.71.12.9323-9332.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stern J. The prospect of domestic bioterrorism. Emerg Infect Dis. 1999 Jul-Aug;5(4):517–522. doi: 10.3201/eid0504.990410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Woodfolk J. A., Sung S. S., Benjamin D. C., Lee J. K., Platts-Mills T. A. Distinct human T cell repertoires mediate immediate and delayed-type hypersensitivity to the Trichophyton antigen, Tri r 2. J Immunol. 2000 Oct 15;165(8):4379–4387. doi: 10.4049/jimmunol.165.8.4379. [DOI] [PubMed] [Google Scholar]
  30. Wright P. J., Warr H. M., Westaway E. G. Comparisons by peptide mapping of proteins specified by Kunjin, West Nile and Murray Valley encephalitis viruses. Aust J Exp Biol Med Sci. 1983 Dec;61(Pt 6):641–653. doi: 10.1038/icb.1983.61. [DOI] [PubMed] [Google Scholar]
  31. Zeng L., Kurane I., Okamoto Y., Ennis F. A., Brinton M. A. Identification of amino acids involved in recognition by dengue virus NS3-specific, HLA-DR15-restricted cytotoxic CD4+ T-cell clones. J Virol. 1996 May;70(5):3108–3117. doi: 10.1128/jvi.70.5.3108-3117.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]

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