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Antibody-Dependent Cellular Cytotoxicity via Humoral Immune Epitope of Nef Protein Expressed on Cell Surface¹

Takeshi Yamada^2,*, Nobukazu Watanabe, Tetsuya Nakamura and Aikichi Iwamoto^3,*,

^* Division of Infectious Diseases, Advanced Clinical Research Center, Division of Cell Processing, and Department of Infectious Disease and Applied Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan

Antibodies against various proteins of HIV type 1 (HIV-1) can be detected in HIV-1-infected individuals. We previously reported that the level of Ab response against one Nef epitope is correlated with HIV-1 disease progression. To elucidate the mechanism for this correlation, we examined Ab-dependent cellular cytotoxicity (ADCC) against target cells expressing Nef. We observed efficient cytotoxicity against Nef-expressing target cells in the presence of patient plasma and PBMCs. This ADCC activity was correlated with the dilution of plasma from HIV-1-infected patients. Addition of a specific synthetic peptide (peptide 31:FLKEKGGLE) corresponding to the Nef epitope reduced cell lysis to 50%. These results suggest that PBMCs of HIV-1-infected patients may exert ADCC via anti-Nef Abs in the patients’ own plasma and serve as a mechanism used by the immune system to regulate HIV-1 replication.

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