HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes

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Cytotoxic T lymphocytes (CTLs) lyse virally infected cells that display viral peptide epitopes in association with major histocompatibility complex (MHC) class I molecules on the cell surface. However, despite a strong CTL response directed against viral epitopes, untreated people infected with the human immunodeficiency virus (HIV-1) develop AIDS. To resolve this enigma, we have examined the ability of CTLs to recognize and kill infected primary T lymphocytes. We found that CTLs inefficiently lysed primary cells infected with HIV-1 if the viral nef gene product was expressed. Resistance of infected cells to CTL killing correlated with nef-mediated downregulation of MHC class I (ref. 1) and could be overcome by adding an excess of the relevant HIV-1 epitope as soluble peptide. Thus, Nef protected infected cells by reducing the epitope density on their surface. This effect of nef may allow evasion of CTL lysis by HIV-1-infected cells.

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Figure 1: Genomic organization of HIV-1 vectors containing PLAP.
Figure 2: Flow-cytometric measurement of anti-HIV CTL-mediated cytotoxicity (clone 161XJA14).
Figure 3: Nef protects cells from killing by the gag-specific CTL clone 18030D23.
Figure 4: Nef protects cells from killing by CTL clone 161JXA14.
Figure 5: Cells infected with the NL-PI HIV-1 molecular clone are protected by Nef against CTL lysis, and CTL killing detected by cytofluorimetry is dependent on expression of the appropriate epitope.


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We thank H. Eisen, H. Ploegh, D. Camerini and members of D.B.'s laboratory; and A. K. Trocha, O. O. Yang, N. Jones and E. Rosenberg for help with culturing CTL clones, for chromium-release assays and for human lymphocytes. K.C. was the recipient of a Howard Hughes fellowship award for physicians. B.K.C. was supported by a Medical Scientist Training Program Award. D.B. is an American Cancer Society Research Professor. Supported at M.I.T. by funds from the Ivan R. Cottrell Chair and at M.G.H. by grants from the N.I.H.

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Correspondence to David Baltimore.

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