Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112)

Tahara‐Hanaoka, Satoko; Shibuya, Kazuko; Onoda, Yuko; Zhang, Hua; Yamazaki, Satoshi; Miyamoto, Akitomo; Honda, Shin‐ichiro; Lanier, Lewis L.; Shibuya, Akira

doi:10.1093/intimm/dxh059

Cited by 248 publications

(223 citation statements)

References 16 publications

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“…These results are consistent with data from Reymond et al who have shown that DNAM-1 binds Necl-5 more efficiently than Nectin-2 and that Necl-5 but not Nectin-2 is the major ligand of DNAM-1 on endothelial cells [30]. Tahara-Hanaoka et al have suggested that DNAM-1 interactions with Nectin-2 may be impaired by homophilic ligation of Nectin-2 [19]. We had already shown that the NK receptor NKG2D was involved in gd T-cell-mediated lysis of HCC cells expressing the corresponding ligands [5].…”

Section: Discussionsupporting

confidence: 92%

“…Our experiments indicate that Necl-5 but not Nectin-2 is involved in the DNAM-1-dependent recognition of tumor cells by gd T cells. Blockade ability of the anti-Nectin-2 mAb (R2.477) was not questioned since this mAb was able to block cytotoxic activity of NK cells against transfectant cells expressing Nectin-2 [19]. These results are consistent with data from Reymond et al who have shown that DNAM-1 binds Necl-5 more efficiently than Nectin-2 and that Necl-5 but not Nectin-2 is the major ligand of DNAM-1 on endothelial cells [30].…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that Necl-5 (also called the poliovirus receptor or CD155) and Nectin-2 (also called the poliovirus-related receptor 2 or CD112) interact with the NK receptor DNAX accessory molecule-1 (DNAM-1 also called CD226) (Fig. 1) [18,19]. The receptor CD96 (Tactile) was identified as an additional receptor for Necl-5 [20].…”

Section: Introductionmentioning

confidence: 99%

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DNAX accessory molecule‐1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vγ9Vδ2 T cells

et al. 2009

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Human Vc9Vd2 T lymphocytes can be activated by nonpeptidic antigens such as the mevalonate pathway-derived isopentenyl pyrophosphate or synthetic phosphoantigen such as bromohydrin pyrophosphate. They display a strong cytotoxic activity against several tumor types, including hepatocellular carcinoma (HCC). Little is known about the mechanisms underlying Vc9Vd2 T-cell recognition of tumor cells, but there is strong evidence that activating NK receptors play a role in cd T-cell cytotoxicity. In this study, we showed that the two NK receptors DNAX accessory molecule-1 (DNAM-1) and CD96 were expressed by Vc9Vd2 T cells. The ligands Nectin-like-5 specific of both DNAM-1 and CD96, and also Nectin-2, an additional ligand of DNAM-1, were present on all HCC cell lines analyzed. Furthermore, we demonstrated by mAb-mediated masking experiments that cytotoxicity against HCC cells as well as IFN-c production in cd T cells were dependent on DNAM-1. Our experiments indicated that Nectin-like-5 but not Nectin-2 was involved in DNAM-1-dependent cd T-cell functions. We did not reveal a role for CD96 in the killing of HCC cells. Finally, we showed by combined mAb-mediated blockade that DNAM-1 and NKG2D could cooperate in the cell lysis of HCC.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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DNAX accessory molecule‐1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vγ9Vδ2 T cells

et al. 2009

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“…It is also known as a costimulatory and adhesion molecule (33, 34) and mediates activation signals for cytotoxicity by CD8 + T cells and NK cells via its binding to CD155, CD112, or both on target cells (35,36). The important function of CD226 is well known as the immune surveillance of tumors (37).…”

Section: Discussionmentioning

confidence: 99%

Increased CD226 Expression on CD8+ T Cells Is Associated with Upregulated Cytokine Production and Endothelial Cell Injury in Patients with Systemic Sclerosis

Ayano

Tsukamoto

Kohno

et al. 2015

The Journal of Immunology

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Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular damage and fibrosis of the skin and internal organs. Because activated and oligoclonally expanded CD8+ T cells can be detected in peripheral blood and lungs of SSc patients, effector memory CD8+ T cells may play a critical role for organ involvement in SSc; however, the pathogenic functions of effector memory CD8+ T cells remain incompletely understood. In this study, we performed DNA microarray analysis of the sort-purified effector memory CD8+ T cells from SSc patients and healthy controls, and showed that the expression of genes related to immune response and cell adhesion, including CD226 (also known as DNAX accessory molecule-1 [DNAM-1]), was significantly altered. Moreover, detailed analysis of CD226 revealed that CD226highCD8+ T cells were increased in SSc patients (mean, 50.7%) compared with healthy controls (32.9%) and were appreciably associated with the severity of skin sclerosis and interstitial lung disease. Furthermore, CD226+CD8+ T cells produced higher amount of various cytokines than CD226− ones, and CD226highCD8+ T cells from SSc patients showed upregulated IL-13 production and positive correlation with the cytotoxic capacity of CD8+ T cells against HUVECs. Finally, the neutralization of CD226 in CD8+ T cells impaired costimulation, cytokine productions, and cytolysis against HUVECs. These findings indicate that upregulated CD226 expression on CD8+ T cells reflects disease severity and is involved in SSc pathogenesis via the production of various cytokines, including profibrotic IL-13 and endothelial cell injury, and that CD226 may be a useful target in the treatment of SSc.

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“…La molécule DNAM-1 est constitutivement exprimée par les cellules NK humaines [6] et les lymphocytes TV9V2 [24]. Elle interagit avec nectine-2 et Necl-5, et favorise ainsi la fonction cytolytique des cellules NK [25,26] (Figure 3). Pour les lymphocytes TV9V2, des expériences menées sur des lignées d'hépatocar-cinome ont révélé que l'engagement de DNAM-1 avec Necl-5 (mais pas avec nectine-2) participe aussi à leur capacité de reconnaissance et de lyse des cellules tumorales.…”

Section: Rôle Des Nectines/nectines-like Dans Le Développement Tumoralunclassified

Les récepteurs de nectines/nectines-likeDNAM-1 et CRTAM

et al. 2014

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Historiquement, PVR (poliovirus receptor) (CD155), aujourd'hui dénommée nectine-like 5 (Necl-5), est la première molécule de la famille des nectines/nectines-like à avoir été caractérisée : c'est le récepteur d'entrée du poliovirus humain. Nectine-1 et nectine-2 ont été les premières nectines isolées, et leur rôle de récepteur dans l'internalisation des virus herpes simplex 1 et 2 a ensuite été démontré. Actuellement, quatre nectines (nectine-1 à -4) et cinq molécules apparentées aux nectines (Necl-1 à -5) ont été identifiées. Leur nomenclature est compliquée du fait que chaque nectine/nectine-like possède plusieurs appellations (voir pour revue [2]). Par exemple, nectine-1 est parfois appelée PRR1 (poliovirus receptor-related protein) ou HVEC (herpes virus entry mediator C). Il faut noter que nectine-4, aussi appelée PVLR4 (poliovirus-receptor-like 4), est éga-lement un des récepteurs d'entrée du virus de la rougeole [3]. Pour Necl-2, plusieurs appellations existent selon la situation biologique dans laquelle son expression a été recherchée : TSLC1 (tumor suppressor in lung cancer 1), IGSF4 (immunoglobulin superfamily member 4), Ra175, SglGSF (spermatogenic immunoglobulin superfamily), ou Syn-CAM1 (synaptic cell adhesion molecule 1). Toutes ces molécules ont une structure similaire ( Figure 1A). Les trois domaines de type Ig-like de la portion extracellulaire -un de type V et deux de type C2 -sont responsables des interactions homophiliques et hétérophiliques des nectines/nectines-like entre elles ou avec leurs ligands, ainsi que de leur dimérisation ( Figure 1B) Les nectines/nectines-like et leurs ligandsLes nectines et nectines-like (Necl) sont des molé-cules dont le nom vient du terme latin necto qui signifie connecter. Elles appartiennent à la superfamille des immunoglobulines (Ig) et ont été initialement décrites pour leur rôle dans les processus d'adhérence indépendants du Ca 2+ [1]. Ce sont des partenaires importants de la formation des jonctions cellulaires dans les tissus épithéliaux et elles participent éga-lement à la polarité cellulaire [2]. Leurs rôles dans la migration cellulaire, l'inhibition de contact, puis la prolifération et la différenciation ont été décrits secondairement. Récemment, la corrélation entre leur surexpression dans les tumeurs ou, au contraire, la perte de leur expression, et le pronostic de ces

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Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112)

Cited by 248 publications

References 16 publications

DNAX accessory molecule‐1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vγ9Vδ2 T cells

DNAX accessory molecule‐1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vγ9Vδ2 T cells

Increased CD226 Expression on CD8+ T Cells Is Associated with Upregulated Cytokine Production and Endothelial Cell Injury in Patients with Systemic Sclerosis

Les récepteurs de nectines/nectines-likeDNAM-1 et CRTAM

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