Inhibition of T-cell activation by syndecan-4 is mediated by CD148 through protein tyrosine phosphatase activity.
Eur J Immunol
; 41(6): 1794-9, 2011 Jun.
Article
en En
| MEDLINE
| ID: mdl-21469128
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Linfocitos T CD4-Positivos
/
Sindecano-4
/
Células Presentadoras de Antígenos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Eur J Immunol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos