Swigut, T., Shohdy, N., Skowronski, J. (April 2001) Mechanism for down-regulation of CD28 by Nef. Embo Journal, 20 (7). pp. 1593-1604. ISSN 0261-4189
Abstract
SIV and HIV Nef proteins disrupt T-cell receptor machinery by down-modulating cell surface expression of CD4 and expression or signaling of CD3-TCR. Nef also down-modulates class I major histocompatibility complex (MHC) surface expression. We show that SIV and HIV-1 Nefs down-modulate CD28, a major co-stimulatory receptor that mediates effective T-cell activation, by accelerating CD28 endocytosis, The effects of Nef on CD28, CD4, CD3 and class I MHC expression are all genetically separable, indicating that all are selected independently. In cells expressing a Nef-green fluorescent protein (GFP) fusion, CD28 co-localizes with the AP-2 clathrin adaptor and Nef-GFP. Mutations that disrupt Nef interaction with AP-2 disrupt CD28 down-regulation. Furthermore, HIV and SIV Nefs use overlapping but distinct target sites in the membrane-proximal region of the CD28 cytoplasmic domain. Thus, Nef probably induces CD28 endocytosis via the AP-2 pathway, and this involves a ternary complex containing Nef, AP-2 and CD28. The likely consequence of the concerted down-regulation of CD28, CD4 and/or CD3 by Nef is disruption of antigen-specific signaling machineries in infected T cells following a productive antigen recognition event.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | AP-2 clathrin adaptor CD28 lentivirus Nef T-cell activation IMMUNODEFICIENCY-VIRUS TYPE-1 T-CELL RECEPTOR CLATHRIN ADAPTER COMPLEXES HIV-1 NEF CD4 ENDOCYTOSIS DILEUCINE MOTIF BINDING SURFACE TRANSGENIC MICE I MOLECULES ZETA-CHAIN |
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organism description > virus > lentivirus |
| CSHL Authors: | |
| Communities: | CSHL labs > Skowronski lab |
| Depositing User: | Matt Covey |
| Date: | April 2001 |
| Date Deposited: | 15 Jan 2014 21:53 |
| Last Modified: | 15 Jan 2014 21:53 |
| PMCID: | PMC145469 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/29313 |
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