A novel function of Siglec-9 A391C polymorphism on T cell receptor signaling.
Int Arch Allergy Immunol
; 154(2): 111-8, 2011.
Article
em En
| MEDLINE
| ID: mdl-20733319
ABSTRACT
BACKGROUND:
Sialic-acid-binding immunoglobulin-like lectins (Siglecs) are the best-characterized immunoglobulin-type lectins. There is a growing amount of data linking Siglec and autoimmune diseases. The recently identified Siglec-9 inhibits T cell receptor (TCR)-mediated signaling which has been demonstrated by site-directed mutagenesis. In human Siglec-9, at least 8 nonsynonymous SNPs have been detected without functional studies. This study examined the SNP(s) related to TCR-mediated signaling.METHODS:
Since the functions of Siglecs are modulated by their interaction with sialic-acid-containing carbohydrate groups, a molecular modeling analysis of carbohydrate binding interactions and an RBC binding analysis were performed using the 8 SNPs. The TCR-mediated signaling was analyzed with the downstream signaling molecules ZAP-70 and IL-2.RESULTS:
This study revealed that an A391C polymorphism is the only mutant related to the binding. Jurkat T cells transfected with the A391C mutant reduced the inhibition of ZAP-70 phosphorylation and IL-2 production compared to cells transfected with the wild type.CONCLUSIONS:
Siglec-9 A391C was the only polymorphism related to TCR-mediated signaling in human Siglec-9, resulting in less inhibition compared to the wild type.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
/
Antígenos CD
/
Lectinas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article