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A viral protein that selectively downregulates ICAM-1 and B7-2 and modulates T cell costimulation
Laurent Coscoy, Don Ganem
Laurent Coscoy, Don Ganem
Published June 15, 2001
Citation Information: J Clin Invest. 2001;107(12):1599-1606. https://doi.org/10.1172/JCI12432.
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A viral protein that selectively downregulates ICAM-1 and B7-2 and modulates T cell costimulation

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Abstract

Kaposi’s sarcoma–associated (KS-associated) herpesvirus (KSHV) is a B-lymphotropic agent linked to AIDS-related lymphoproliferative disorders and KS. We and others have earlier identified two viral genes, K3 and K5, that encode endoplasmic reticulum proteins that downregulate surface MHC-I chains by enhancing their endocytosis. Here we have examined the ability of these proteins to influence the disposition of other host surface proteins implicated in immune recognition and activation. We report that K5, but not K3, expression in BJAB cells dramatically reduces ICAM-1 and B7-2 surface expression; B7-1 expression is unaffected. This K5-induced reduction can be reversed by coexpression of a dominant negative mutant of dynamin, indicating that the loss of ICAM and B7-2 surface expression is due to their enhanced endocytosis. This downregulation is functionally significant, because K5-transfected B cells show substantial impairment in their ability to induce T cell activation. K5 is thus the first example of a viral modulator of immunological synapse formation and T cell costimulation. We propose that its expression reduces T cell responses to KSHV-infected B cells early in infection, thereby diminishing antiviral cytokine release and the production of stimulatory signals for CTL generation.

Authors

Laurent Coscoy, Don Ganem

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Figure 3

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T cell activation by K5 expressing BJAB cells. (a) Twenty-four hours aft...
T cell activation by K5 expressing BJAB cells. (a) Twenty-four hours after transfection with a RE/AP reporter plasmid, Jurkat cells were stimulated by incubation with BJAB cells and SEE. Jurkat activation was quantified by luciferase assays 16 hours after stimulation. Each luciferase assay was done in triplicate on at least three different independent transfection experiments. For blocking conditions, BJAB cells were preincubated with Ab’s 30 minutes before addition of Jurkat cells and SEE. (b) Jurkat cells were transfected with NFAT, AP-1, or NF-κB reporter plasmid and stimulated as in a. Stimulation with TPA/ionomycin was used as positive control. (c) Jurkat cells were left unstimulated, stimulated with PMA/iono, or stimulated with BJAB cells and SEE. After 16 hours, cells were stained with an R-phycoerythrin–conjugated anti-CD19 Ab and a fluorescein-conjugated anti-CD69 Ab. Jurkat cells were identified as being negative for CD19 (a B cell marker, present at the cell surface of BJAB cells). Histograms represent CD69 expression on Jurkat cells.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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