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Antibody-dependent cell-mediated cytotoxicity directed by a human monoclonal antibody reactive with gp120 of HIV-1

Koup, Richard A.; Robinson, James E.; Nguyen, Quoc V.; Pikora, Cheryl A.; Blais, Bruce; Roskey, Allysen; Panicali, Dennis; Sullivan, John L.
ORIGINAL PAPERS AND SHORT COMMUNICATIONS: Basic Science: PDF Only

We used a human monoclonal antibody (MAb; 15e) to identify an antibody-dependent cell-mediated cytotoxicity (ADCC) epitope on HIV-1 gp120. 15e has been shown to recognize a conformation-dependent epitope on gp120 which is important in both CD4 binding and neutralizing of HIV-1 infection. 15e binds to gp120 of HIV-1IIIB but not HIV-1RF. Using a standard ADCC assay, I5e was found to mediate ADCC against cells infected with HIV-1IIIB but not HIV-1RF. l5e did not mediate ADCC against cells with recombinant gpl20 bound to surface CD4, indicating that l5e does not mediate innocent bystander ADCC against uninfected CD4 cells. To better define the l5e epitope, we performed ADCC against target cells infected with a vaccinia vector which expresses processed HIV-1IIIB gpl60 from which the third variable region was deleted (amino acids, 312–328). MAb l5e efficiently mediated ADCC against cells expressing this altered form of gpl20, indicating that this region is not contributing to the conformational epitope defined by l5e. l5e defines an important epitope in the human immune response to HIV-1 infection. Antibodies with l5e-like activity may be useful in immunoprophylaxis or immunotherapy of HIV-1 infection.

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