The LFA-1-associated Molecule PTA-1 (CD226) on T Cells Forms a Dynamic Molecular Complex with Protein 4.1G and Human Discs Large

Ralston, Kylie J.; Hird, Samantha L.; Zhang, Xinhai; Scott, Judith L.; Jin, Boquan; Thorne, Rick F.; Berndt, Michael C.; Boyd, Andrew W.; Burns, Gordon F.

doi:10.1074/jbc.m401040200

Cited by 60 publications

(49 citation statements)

References 82 publications

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“…DNAM-1 is a 65 kDa transmembrane glycoprotein physically and functionally associated with lymphocyte functionassociated antigen-1 (LFA-1) [22]. DNAM-1 engagement by mAbmediated cross-linking triggers tyrosine phosphorylation and its recruitment into the membrane rafts [23,24]. Moreover, DNAM-1 functions such as adhesion are dependent on the phosphorylation of serine residue 329 in the cytoplasmic domain by the PKC [25].…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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

et al. 2009

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“…However, our latest experiments do not suggest a role for 4.1G in FcgRI membrane stabilization in unstimulated cells (C. E. van der Poel and J. H. W. Leusen, unpublished observations). Alternatively, 4.1G might be involved in FcgRI signaling as 4.1G, and the highly homologous 4.1R have been implicated in T cell signaling (33,34).…”

Section: Interactors Of the Fcgri Ligand-binding A-chainmentioning

confidence: 99%

Functional Characteristics of the High Affinity IgG Receptor, FcγRI

Poel¹,

Spaapen

Winkel

et al. 2011

The Journal of Immunology

149

114

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IgG FcRs are important mediators of immunity and play a key role during Ab-based immunotherapy. Within the leukocyte IgG receptor family, only FcγRI is capable of IgG binding with high affinity. FcγRI exists as a complex of a ligand binding α-chain and an FcR γ-chain. The receptors’ α-chain can, furthermore, elicit several functions independent of the ITAM-bearing FcR γ-chain. Functional implications of high-affinity IgG binding and mechanisms underlying FcR γ-chain–independent signaling remain unclear to this day. In this paper, we provide an overview of past literature on FcγRI and address the implications of recently described interactions between cytosolic proteins and the FcγRI α-chain, as well as cytokine-enhanced FcγRI immune complex binding. Furthermore, an analysis of potential polymorphisms within the FCGR1A gene is provided.

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“…In humans, CD226 is constitutively expressed in hematopoietic cells such as T cells, NK cells, NKT cells, a subset of B cells, monocytes/macrophages, and dendritic cells and is involved in a variety of immunological functions, including T cell differentiation and cytotoxicity, NK cell cytotoxicity, NKT cell apoptosis, monocyte extravasation, and dendritic cell maturation (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

Expression of CD226 Antagonizes Apoptotic Cell Death in Murine Thymocytes

Fang¹,

Zhang

Miao³

et al. 2009

The Journal of Immunology

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*CD226 is known to be expressed on many types of peripheral lymphoid cells and involved in T cell differentiation, activation, and cytotoxicity. In this study, we report that CD226 is also expressed on mouse thymocytes at varying developmental stages, and its expression is associated with resistance of thymocytes to apoptosis. The levels of CD226 expression appeared to be closely coupled with thymocyte development, in that it was preferentially expressed on CD4 ؉ CD8 ؊ and CD4 ؊ CD8 ؉ thymocytes at all stages during mouse development, and was markedly increased on the cells in neonatal mice. Of the CD4 ؉ CD8 ؉ population, CD226 was predominantly expressed by the cells also positive for CD69, suggesting that CD226 expression may be induced in thymocytepositive selection. Inhibition of CD226 by short hairpin RNA in a fetal thymus organ culture model led to reduced thymus cellularity, which was associated with enhanced apoptotic cell death. In contrast, CD226-transgenic mice displayed enlarged thymus lobes resulting from increased thymus cellularity. T he CD226, also named TliSA1, PTA1, or DNAM-1, is a member of the Ig superfamily containing two Ig V-like domains in its extracellular region and three tyrosine residues in its cytoplasmic portion (1, 2). In humans, CD226 is constitutively expressed in hematopoietic cells such as T cells, NK cells, NKT cells, a subset of B cells, monocytes/macrophages, and dendritic cells and is involved in a variety of immunological functions, including T cell differentiation and cytotoxicity, NK cell cytotoxicity, NKT cell apoptosis, monocyte extravasation, and dendritic cell maturation (1-12).In the murine system, engagement of CD226 with its ligands (mCD112 and Tage4) is believed to mediate a costimulatory signal in Ag-specific T cells (13). It has been reported that Th1 cells differentiation are involved in increased levels of CD226 expression, whereas the levels of CD226 were down-regulated upon Th2 cell polarization in BALB/c mice. In addition, treatment with a specific mAb against CD226(10E5) was shown to inhibit T cell proliferation in spleens and lymph nodes in SJL/J mice (14).Thymus is an organ for T lymphocyte development from early thymocyte progenitors to functional competent T cells ready for emigration to the periphery. To date, there has been no report on the expression status and the potential functional significance of CD226 in thymocytes. In view of this, we have examined the expression levels of CD226 on thymocytes during mouse development. We show in this report that CD226 is preferentially expressed on CD4 ϩ CD8 Ϫ and CD4 Ϫ CD8 ϩ thymocytes at all stages during mouse development and is markedly increased in the cells in neonatal mice. Of the CD4 ϩ CD8 ϩ population, CD226 is predominantly expressed by the cells also positive for CD69. Moreover, we demonstrate that CD226 is an antiapoptotic molecule that may play an important role in regulating thymus cellularity during murine development. Materials and Methods Cell culture and AbThe EL-4 thymoma cell line and the...

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The LFA-1-associated Molecule PTA-1 (CD226) on T Cells Forms a Dynamic Molecular Complex with Protein 4.1G and Human Discs Large

Cited by 60 publications

References 82 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

Functional Characteristics of the High Affinity IgG Receptor, FcγRI

Expression of CD226 Antagonizes Apoptotic Cell Death in Murine Thymocytes

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