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Eur J Immunol. 2011 Jun;41(6):1794-9. doi: 10.1002/eji.201041233. Epub 2011 May 9.

Inhibition of T-cell activation by syndecan-4 is mediated by CD148 through protein tyrosine phosphatase activity.

Author information

  • 1Department of Dermatology, The University of Texas Southwestern Medical Center and Dermatology Section (Medical Service), Dallas Veterans Affairs Medical Center, Dallas, TX, USA.

Abstract

Most coinhibitory receptors regulate T-cell responses through an ITIM that recruits protein tyrosine phosphatases (PTPs) to mediate inhibitory function. Because syndecan-4 (SD-4), the coinhibitor for DC-associated heparan sulfate proteoglycan integrin ligand (DC-HIL), lacks such an ITIM, we posited that SD-4 links with a PTP in an ITIM-independent manner. We show that SD-4 associates constitutively with the intracellular protein syntenin but not with the receptor-like PTP CD148 on human CD4(+) T cells. Binding to DC-HIL allowed SD-4 to assemble with CD148 through the help of syntenin as a bridge, and this process upregulated the PTP activity of CD148, which is required for SD-4 to mediate DC-HIL's inhibitory function. Using a mouse model, we found SD-4 to be located away from the immunological synapse formed between T cells and APCs during activation of T cells. These findings indicate that SD-4 is unique among known T-cell coinhibitors, in employing CD148 to inhibit T-cell activation at a site distal from the synapse.

Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID:
21469128
[PubMed - indexed for MEDLINE]
PMCID:
PMC3128389
Free PMC Article

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