Inhibition of HIV-1 rgp120 binding to CD4+ T cells by monoclonal antibodies directed against the gp120 C1 or C4 region.
Reagents which block the interaction of HIV-1 gp120 with CD4+ T cell are of therapeutic interest. We assessed the ability of the murine monoclonal antibody (mAb) 87-135/9 to bind to the rgp120 C1 region and to block the CD4 interaction, and compared this with the reactivity of the rat mAb 388/389 or the human mAbs F105 and b12, which are known to bind within or near the gp120 C4 region. ELISA and surface plasmon resonance measurements showed that mAb 87-135/9 recognized specifically the gp120 C1 peptide HEDIISLWDQSLK (residues 105-117). All four mAbs bound to rgp120 and blocked its interaction with CD4+ T cells. When mAb 87-135/9 was used in combination with one of the other antibodies, its inhibitory effect was additive. A therapeutic approach could be to use a human anti-gp120/CD4bs conformational mAb in combination with a humanized Ab directed against the conserved, linear gp120 C1 epitope and/or an anti-viral drug to hinder the HIV-1 virus and shedded envelope protein to bind to CD4+ T cells.
Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Germany. m.kroepelin@dkfz-heidelberg.de
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Kröpelin
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Süsal
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Daniel
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Opelz
D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001666:Binding Sites, Antibody; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015483:HIV Antibodies / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism*
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059760:HIV envelope protein gp120 (55-65); D010446:Peptide Fragments; D011994:Recombinant Proteins