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

Collins, Kathleen L. and Chen, Benjamin K. and Kalams, Spyros A. and Walker, Bruce D. and Baltimore, David (1998) HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature, 391 (6665). pp. 397-401. ISSN 0028-0836. doi:10.1038/34929.

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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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Baltimore, David0000-0001-8723-8190
Additional Information:© 1998 Macmillan Publishers Ltd. Received 17 September 1997; Accepted 27 October 1997; Issue Date 22 January 1998. 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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Howard Hughes Medical Institute (HHMI)UNSPECIFIED
American Cancer SocietyUNSPECIFIED
Massachusetts Institute of Technology (MIT)UNSPECIFIED
Issue or Number:6665
Record Number:CaltechAUTHORS:20200507-103823040
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Official Citation:Collins, K., Chen, B., Kalams, S. et al. HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 391, 397–401 (1998).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103067
Deposited By: Tony Diaz
Deposited On:08 May 2020 18:07
Last Modified:16 Nov 2021 18:18

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