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Identification of epitopes recognized by monoclonal antibodies directed against HTLV-I envelope surface glycoprotein using peptide phage display

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Abstract

Phage peptide libraries constitute powerful tools for themapping of epitopes recognized by monoclonal antibodies (mAbs).Using screening of phage displayed random peptide libraries wehave characterized the binding epitopes of three mAbs directedagainst the surface envelope glycoprotein (gp46) of the humanT-cell leukemia virus type I (HTLV-I). Two phage libraries,displaying random heptapeptides with or without flankingcysteine residues, were screened for binding to mAbs 7G5D8, DB4and 4F5F6. The SSSSTPL consensus sequence isolated fromconstrained heptapeptide library defines the epitope recognizedby DB4 mAb and corresponds to the exact region 249–252 of thevirus sequence. The APPMLPH consensus sequence isolated fromnon constrained heptapeptide library defines the epitoperecognized by 7G5D8 mAb and corresponds to the region 187–193with a single amino acid substitution, methionine to leucine atposition 190. The third consensus sequence LYWPHD isolated fromconstrained heptapeptide library defines the epitope recognizedby 4F5F6 mAb. It corresponds to an epitope without directequivalence with the virus sequence. The data presented hereshowed that 7G5D8 and DB4 mAbs are raised against linearepitopes while 4F5F6 mAb recognized a continuous topographic epitope.

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References

  1. Poiesz, B.J., Ruscetti, F.W., Gazdar, A.F., Bunn, P.A., Minna, J.D. and Gallo, R.C., Detection and isolation of type C retroviruses particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc. Natl. Acad. Sci. U.S.A., 77 (1980) 7415.

    Google Scholar 

  2. Miyoshi, I., Kubonishi, I., Yoshimoto, S., Akagi, T., Ohtsuki, Y., Shiraishi, Y., Nagata, K. and Hinuma, Y., Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukemic T-cells. Nature, 294 (1981) 770.

    Google Scholar 

  3. Gessain, A., Barin, F., Vernant, J.C., Gout, O., Maurs, L., Calender, A. and De Thé, G., Antibodies to human Tlymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet, 2 (1985) 407.

    Google Scholar 

  4. Osame, M., Matsumoto, M., Usuku, K., Izumo, S., Ijichi, N., Amitani, H., Tara, M. and Igata, A., Chronic progressive myelopathy associated with elevated antibodies to human Tlymphotropic virus type 1 and adult T-cell leukemialike cells. Ann. Neurol., 21 (1987) 117.

    Google Scholar 

  5. Shida, H., Tochikura, T., Sato, T., Konno, T., Hirayoshi, K., Seki, M., Ito, Y., Hatanaka, M., Hinuma, Y., Sugimoto, M., Takahashi-Nishimaki, F., Maruyama, T., Miki, K., Suzuki, K., Morita, M., Sashiyama, H. and Hayami, M., Effect of the recombinant vaccinia viruses that express HTLV-I envelope glycoprotein on HTLV-I infection. EMBO J., 6 (1987) 3379.

    Google Scholar 

  6. Nakamura, H., Hayami, M., Ohta, Y., Ishikawa, K.I., Tsujimoto, H., Kiyokawa, T., Yoshida, M., Sasagawa, A. and Honjo, S., Protection of cynomologus monkeys against infection by human T-cell leukemia virus type-I by immunization with viral env gene products produced in Escherichia coli. Int. J. Cancer, 40 (1987) 403.

    Google Scholar 

  7. Yamamoto, N., Schneider, J., Koyanagi, Y., Hinuma, Y. and Hunsmann, G., Adult T-cell leukemia (ATL) virus-specific antibodies in ATL patients and healthy virus carriers. Int. J. Cancer, 32 (1983) 281.

    Google Scholar 

  8. Tanaka, Y., Zeng, L., Shiraki, H., Shida, H. and Tozawa, H., Identification of a neutralization epitope on the envelope gp46 antigen of human T-cell leukemia virus type I and induction of neutralizing antibody by peptide immunization. J. Immunol., 147 (1991) 354.

    Google Scholar 

  9. Astier-Gin, T., Portail, J.P., Lafond, B. and Guillemain, B., Identification of HTLV-I-or HTLV-II-producing cells by cocultivation with BHK-21 cells stably transfected with a LTR-lacZ gene conctruct. J. Virol. Meth., 51 (1995) 19.

    Google Scholar 

  10. Horal, P., Hall, W.W., Svennerholm, B., Lycke, J., Jeansson, S., Rymo, L., Kaplan, M.H. and Vahlne, A., Identification of type-specific linear epitopes in the glycoproteins gp46 and gp21 of human T-cell leukemia viruses type I and type II using synthetic peptides. Proc. Natl. Acad. Sci. U.S.A., 88 (1991) 5754.

    Google Scholar 

  11. Londos-Gagliardi, D., Jauvin, V., Armengaut, M.H., Astier-Gin, T., Goetz, M., Huet, S. and Guillemain, B., Influence of amino acid substitutions on antigenicity of immunodominant regions of the HTLV type I envelope surface gylcoprotein: A study using monoclonal antibodies raised against relevant peptides. AIDS Res. Hum. Retroviruses, 15 (1999) 909.

    Google Scholar 

  12. Blanchard, S., Astier-Gin, T., Moynet, D., Edouard, E. and Guillemain, B., Different neutralization patterns among sera of patients infected with cosmopolitan HTLV-I. Virology, 245 (1998) 90.

    Google Scholar 

  13. Tallet, B., Astier-Gin, T., Moynet, D., Londos-Gagliardi, D. and Guillemain, B., Sequence variation in the NH2 and carboxy terminal part of the HTLV-I gp46 induce specific neutralizing antibodies. AIDS Res. Hum. Retroviruses, 17 (2001) 337.

    Google Scholar 

  14. Edouard, E., Legrand, E., Astier-Gin, T., Dalibart, R., Geoffre, S., Dalbon, P., Guillemain, B. and Londos-Gagliardi, D., Characterization of monoclonal antibodies directed against the gp46 of human T-cell leukemia virus type I (HTLV-I). Leukemia, 8 (1994) S60.

    Google Scholar 

  15. Londos-Gagliardi, D., Armengaud, M.-H., Freund, F., Dalibart, R., Moze, E., Huet, S., Legrand, E. and Guillemain, B.J., Antibodies directed against a variable and neutralizable region of the HTLV-I envelope surface glycoprotein. Leukemia, 11 (1997) 38.

    Google Scholar 

  16. Morris, G.E., ‘Overview: Choosing a Method for Epitope Mapping’, In: Glenn E. Morris (ed.), Methods in Molecular Biology, Epitope Mapping Protocols, Humana Press, Totowa, New Jersey, 1996, pp. 1–9.

    Google Scholar 

  17. Fack, F., Hügle-Dörr, B., Song, D., Queitsch, I., Petersen, G. and Bautz, E.K.F., Epitope mapping by phage display: Random versus gene-fragment libraries. J. Immunol.Methods, 206 (1997) 43.

    Google Scholar 

  18. Smith, G., Filamentous fusion phage: Novel expression vectors that display cloned antigens on the surface of the virion. Science, 228 (1985) 1315.

    Google Scholar 

  19. Germaschewski, V. and Murray, K., Screening a monoclonal antibody with a fusion-phage display library shows a discontinuity in a linear epitope within PreS1 of hepatitis B virus. J. Med. Virol., 45 (1995) 300.

    Google Scholar 

  20. Valadon, P., Nussbaum, G., Boyd, L.F., Margulies, D.H. and Scharff, M.D., Peptide libraries define the fine specificity of anti-polysaccharide antibodies to Cryptococcus neoformans. J. Mol. Biol., 261 (1996) 11.

    Google Scholar 

  21. Cook, A.D., Davies, J.M., Myers, M.A., Mackay, I.R. and Rowley, M.J., Mimotopes identified by phage display for the monoclonal antibody CII-CI to type II collagen. J. Autoimmunity, 11 (1998) 205.

    Google Scholar 

  22. Dybwad, A., Bogen, B., Natvig, J.B., Forre, O. and Sioud, M., Peptide phage libraries can be an efficient tool for identifying antibody ligands for polyclonal antisera. Clin. Exp. Immunol., 102 (1995) 438.

    Google Scholar 

  23. Pereboeva, L.A., Pereboeva, A.V. and Morris, G.E., Identification of antigenic sites on three hepatitis C virus proteins using phage-displayed peptide libraries. J. Med. Virol., 56 (1998) 105.

    Google Scholar 

  24. Nicot, C., Astier-Gin, T., Edouard, E., Legrand, E., Moynet, D., Vital, A., Londos-Gagliardi, D., Moreau, J.P. and Guillemain, B., Establishment of HTLV-I infected cell lines from French, Guianese and West Indian patients and isolation of a proviral clone producing viral particles. Virus Res., 30 (1993) 317.

    Google Scholar 

  25. Gray, G.S., Bartman, T. and White, M., Nucleotide sequence of the core (gag) gene from HTLV-1 isolate MT-2. Nucleic Acids Research, 17 (1989) 7998.

    Google Scholar 

  26. Malik, K.T.A., Even, J. and Karpas, A.: Molecular cloning and complete nucleotide sequence of an adult T-cell leukemia virus/human T-cell leukemia virus type I (ATLV/HTLV-I) isolate of Caribbean origin: Relationship to other members of the ATLV/HTLV-I subgroup. J. Gen. Virol., 69 (1988) 1695.

    Google Scholar 

  27. McLafferty, M.A., Kent, R.B., Ladner, R.C. and Markland, W., M13 bacteriophage displaying disulfide-constrained microproteins, Gene, 128 (1993) 29.

    Google Scholar 

  28. Hopp, T.P. and Woods, K.R., Prediction of protein antigenic determinants from amino acid sequences. Proc. Natl. Acad. Sci. U.S.A., 78 (1981) 3824.

    Google Scholar 

  29. Londos-Gagliardi, D., Dalibart, R., Geoffre, S., Dalbon, P., Pouliquen, J.F., Georges-Courbot, M.C., Sainte-Foie, S., Hajjar, C., Georges, A.J., Moreau, J.P. and Guillemain, B., Immunogenenicity of variable regions of surface envelope glycoprotein of HTLV type I and identification of new major epitopes in the 239-261 region. AIDS Res. Hum. Retroviruses, 12 (1996) 941.

    Google Scholar 

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Chagnaud, J.L., Moynet, D., Londos-Gagliardi, D. et al. Identification of epitopes recognized by monoclonal antibodies directed against HTLV-I envelope surface glycoprotein using peptide phage display. Letters in Peptide Science 8, 95–106 (2001). https://doi.org/10.1023/A:1015093204280

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