A Novel Function of Siglec-9 A391C Polymorphism on T Cell Receptor Signaling
- Authors
- Cheong, Kyung Ah; Chang, Yoon-Seok; Roh, Joo Young; Kim, Bum-Jun; Kim, Myung-Nam; Park, Youn Min; Park, Hai Jin; Kim, Nam-Doo; Lee, Chang-Hoon; Lee, Ai-Young
- Issue Date
- Jan-2011
- Publisher
- KARGER
- Keywords
- Siglec-9; Homology structure model; Red blood cell binding; T cell receptor-mediated signaling; A391C polymorphism
- Citation
- INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, v.154, no.2, pp 111 - 118
- Pages
- 8
- Journal Title
- INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY
- Volume
- 154
- Number
- 2
- Start Page
- 111
- End Page
- 118
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/21956
- DOI
- 10.1159/000320225
- ISSN
- 1018-2438
1423-0097
- 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. Copyright (C) 2010 S. Karger AG, Basel
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