Immunogenicity of Synthetic Peptides Corresponding to Various Epitopes of the Human Immunodeficiency Virus Envelope Protein

  • Habib Zaghouani
  • Brenda Hall
  • Himanshu Shah
  • Constantin Bona
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 303)

Abstract

The envelope gene of the human immunodeficiency virus (HIV) encodes a 160 kd precursor protein which during virus maturation is cleaved into 120 kd and 41 kd proteins, respectively 1,2. The outer (gp120) and the transmembrane (gp41) proteins are non-covalently associated and are involved in virus infectivity 3-6. The gp120 has been suggested to bear the CD4 binding site mediating the attachment of the virus to the CD4 antigen 4,7. Recently, using deletion mutants8 and monoclonal antibodies9 the CD4 binding site was mapped within the amino acid sequence 420–437 of the gp120 protein. The comparison of sequences among the fusogenic sites of various viruses with the sequence of HIV predicted that the sequence 526-535 of the amino terminal part of gp41 to be the fusogenic site of HIV-I10. Beside these sites playing an important role in infectivity, the gp160 protein bears B cell epitopes inducing neutralizing antibodies and T cell epitopes recognized by T helper and cytotoxic T cells (data reviewed in 11). To date, the best characterized neutralizing epitope is the so called principle neutralizing determinant or PND which maps within the cysteine loop of the gp120 protein 12,13. It has been suggested that the hexapeptide, GPGRAF, which is conserved in the majority of known HIV-1 isolates is responsible for the induction of broadly neutralizing antibodies14. Recently, it was shown that the peptide corresponding to amino acid residues 254–274 of gp120 represents an immunodominant epitope capable of inducing antibodies in HIV-1 infected patients15. Also the C-terminal peptide 504–518 of gp120 reacted with sera of HIV-infected patients16. In the present work, we present data on the immunogenicity of 4 peptides corresponding to various epitopes of the gp160 protein in various animal species.

Keywords

Hepatitis Tyrosine Iodine Cysteine Lysine 

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References

  1. 1.
    J.S. Allan, J.E. Coligan, F. Barin, M.F. McLane, J.G. Sodroski, C.A. Rosen, W.A. Haseltine, T-H. Lee, and M. Essex, Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III,Sci. 228:1091–1093 (1985).CrossRefGoogle Scholar
  2. 2.
    F.D. Veronese, A.L. DeVico, T.D. Copeland, S. Oroszlan, R.C. Gallo, and M.G. Sarngadharan, Characterization of gp41 as the transmembrane protein coded by the HTLV-III/LAV envelope gene,Sci. 229:1402–1405 (1985).CrossRefGoogle Scholar
  3. 3.
    J.M. McCune, L.B. Rabin, M.B. Feinberg, M. Lieberman, J.C. Kosek, G.R. Reyes, and I.L. Weissman, Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus, Cell 53:55–67 (1988).PubMedCrossRefGoogle Scholar
  4. 4.
    J.S. McDougal, M.S. Kennedy, J.M. Sligh, S.P. Cort, A. Mawle, and J.K.A. Nicholson, Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule,Sci. 231:382–385 (1986).CrossRefGoogle Scholar
  5. 5.
    B.S. Stein, S.D. Gowda, J.D. Lifson, R.C. Penhallow, K.G. Bensch, and E.G. Engleman, pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane, Cell 49:659–668 (1987).PubMedCrossRefGoogle Scholar
  6. 6.
    M. Kowalski, J. Potz, L. Basiripour, T. Dorfman, W.C. Goh, E. Terwilliger, A. Dayton, C. Rosen, W. Haseltine, and J. Sodroski, Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1,Sci. 237:1351–1355 (1987).CrossRefGoogle Scholar
  7. 7.
    A.G. Dalgleish, P.C.L. Beverly, P.R. Clapham, D.H. Crawford, M.F. Graves, and R.A. Weiss, The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus, Nature (London) 312:763–767 (1984).CrossRefGoogle Scholar
  8. 8.
    L.A. Lasky, G. Nakamura, D.H. Smith, C. Fennie, C. Shimasaki, E. Patzer, P. Berman, T. Gregory, and D. Capon, Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor, Cell 50:975–985 (1987).PubMedCrossRefGoogle Scholar
  9. 9.
    N. Sun, D.D. Ho, C.R.Y. Sun, R. Liou, W. Gordon, M.S.C. Fung, X. Li, R.C. Ting, T-H. Lee, N.T. Chang, and T-W. Chang, Generation and characterization of monoclonal antibodies to the putative CD4-binding domain of human immunodeficiency virus type 1 gp120, J. Virol. 63:3579–3585 (1989).PubMedGoogle Scholar
  10. 10.
    W.R. Gallaher, J.M. Ball, R.F. Garry, M.C. Griffin, and R.C. Montelaro, A general model for the transmembrane proteins of HIV and other retroviruses, AIDS Res. Hum. Retroviruses 5:431–440 (1989).PubMedCrossRefGoogle Scholar
  11. 11.
    Q.J. Sattentau, HIV infection and the immune system, Biochimica et Biophysica Acta 989:255–268 (1989).PubMedGoogle Scholar
  12. 12.
    G. Goudsmit, C. Debouck, R.H. Meloen, L. Smit, M. Bakker, D.M. Asher, A.V. Wolff, C.J. Gibbs, and C. Gajdusek, Human immunodeficiency virus type 1 neutralization epitope with conserved architecture elicits early type-specific antibodies in experimentally infected chimpanzees, Proc. Natl. Acad. Sci. USA 85:4478–4482 (1988).PubMedCrossRefGoogle Scholar
  13. 13.
    G.J. LaRosa, J.P. Davide, K. Weinhold, J.A. Waterbury, A.T. Profy, J.A. Lewis, A.J. Langlois, G.R. Dreesman, R.N. Boswell, P. Shadduck, L.H. Holley, M. Karplus, D.P. Bolognesi, T.J. Matthews, E.A. Emini, and S. D. Putney, Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant,Sci. 249:932–935 (1990).CrossRefGoogle Scholar
  14. 14.
    K. Javaherian, A.J. Langlois, G.J. LaRosa, A.T. Profy, D.P. Bolognesi, W.C. Herlihy, S.D. Putney, and T.J. Matthews, Broadly neutralizing antibodies elicited by the hypervariable neutralizing determinant of HIV-1,Sci. 250:1590–1593 (1990).CrossRefGoogle Scholar
  15. 15.
    D.D. Ho, J.C. Kaplan, I.E. Rackauskas, and M.E. Gurney, Second conserved domain of gp120 is important for HIV infectivity and antibody neutralization,Sci. 239:1020–1023 (1988).CrossRefGoogle Scholar
  16. 16.
    T.J. Palker, M.E. Clark, A.J. Langlois, T.J. Matthews, K.J. Weinhold, R.R. Randall, D.P. Bolognesi, and B.F. Haynes, Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides, Proc. Natl. Acad. Sci. USA 85:1932–1936 (1988).PubMedCrossRefGoogle Scholar
  17. 17.
    F-T. Liu, M. Zinnecker, T. Hamaoka, and D.H. Katz, New procedures for preparation and isolation of conjugates of proteins and a synthetic copolymer of D-amino acids and immunochemical characterization of such conjugates, Biochemistry 18:690–697 (1979).PubMedCrossRefGoogle Scholar
  18. 18.
    A. Nixon-George, T. Moran, G. Dionne, C.L. Penney, D. Lafleur, and C.A. Bona, The adjuvant effect of stearyl tyrosine on a recombinant subunit hepatitis B surface antigen,J. Immunol. 144:4798–4802 (1990).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Habib Zaghouani
    • 1
  • Brenda Hall
    • 1
  • Himanshu Shah
    • 1
  • Constantin Bona
    • 1
  1. 1.Department of MicrobiologyMount Sinai School of MedicineNew YorkUSA

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