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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2678-2686.
Prepublished online as a Blood First Edition Paper on June 22, 2006; DOI 10.1182/blood-2006-04-015404.
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Submitted April 10, 2006
Accepted June 7, 2006
DIgR2, dendritic cell-derived immunoglobulin receptor 2, is one representative of a family of IgSF inhibitory receptors and mediates negative regulation of dendritic cell-initiated antigen-specific T cell responses
Liyun Shi, Kun Luo, Dajing Xia, Taoyong Chen, Guoyou Chen, Yingming Jiang, Nan Li, and Xuetao Cao*
Institute of Immunology, Zhejiang University,P.R.China
The Institute of Immunology, Second Military Medical University, Shanghai, P.R.China
* Corresponding author; email: caoxt{at}public3.sta.net.cn.
Dendritic cells (DCs) are specialized antigen-presenting cells that play crucial roles in the initiation and regulation of immune responses. Maturation and activation of DCs are controlled by a balance of the inhibitory and activating signals transduced through distinct surface receptors. Many inhibitory receptors expressed by DCs have been identified while the new members and their functions need further investigation. In this study, we functionally characterized DIgR2 (DC-derived immunoglobulin receptor 2) as a novel representative of a family of inhibitory receptors belonging to the immunoglobulin superfamily. We show that DIgR2 contains two immunoreceptor tyrosine-based inhibitory motifs (ITIM) within its cytoplasmic region and that DIgR2 associates with Src homology-2 domain-containing protein tyrosine phosphatases-1 (SHP-1). Blockade of DIgR2 on DCs by pretreatment with DIgR2-Ig fusion protein or by silencing with specific small interfering RNA enhances DC-initiated T cell proliferation and antigen-specific T cell responses both in vitro and in vivo. Furthermore, immunization of mice with antigen-pulsed, DIgR2-silenced DCs elicits more potent antigen-specific CD4+ and CD8+ T cell responses, thus protecting the vaccinated mice from tumor challenge more effectively. Our data suggest that DIgR2 is a functionally inhibitory receptor and can mediate negative signaling to regulate DC-initiated antigen-specific T cell responses.

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