CD226 Protein Is Involved in Immune Synapse Formation and Triggers Natural Killer (NK) Cell Activation via Its First Extracellular Domain

Hou, Shengke; Ge, Kuikui; Zheng, Xiaodong; Wei, Haiming; Sun, Rui; Tian, Zhigang

doi:10.1074/jbc.m113.498253

Cited by 28 publications

(32 citation statements)

References 37 publications

(38 reference statements)

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“…In such situations, TCR‐NK cells could retain their capacity to recognize and eliminate targets on the basis of missing‐self recognition . The conservation of NK activity in TCR‐NK cells is supported by the observation that they retain their original ability to respond to K562 targets potentially through engagement of NK cell activating receptors such as NKp30, NKp44, and DNAM‐1 (Fig. B).…”

Section: Discussionmentioning

confidence: 88%

Engineering antigen‐specific NK cell lines against the melanoma‐associated antigen tyrosinase via TCR gene transfer

et al. 2019

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Introduction of Chimeric Antigen Receptors to NK cells has so far been the main practical method for targeting NK cells to specific surface antigens. In contrast, T cell receptor (TCR) gene delivery can supply large populations of cytotoxic T‐lymphocytes (CTL) targeted against intracellular antigens. However, a major barrier in the development of safe CTL‐TCR therapies exists, wherein the mispairing of endogenous and genetically transferred TCR subunits leads to formation of TCRs with off‐target specificity. To overcome this and enable specific intracellular antigen targeting, we have tested the use of NK cells for TCR gene transfer to human cells. Our results show that ectopic expression of TCR α/β chains, along with CD3 subunits, enables the functional expression of an antigen‐specific TCR complex on NK cell lines NK‐92 and YTS, demonstrated by using a TCR against the HLA‐A2‐restricted tyrosinase‐derived melanoma epitope, Tyr368‐377. Most importantly, the introduction of a TCR complex to NK cell lines enables MHC‐restricted, antigen‐specific killing of tumor cells both in vitro and in vivo. Targeting of NK cells via TCR gene delivery stands out as a novel tool in the field of adoptive immunotherapy which can also overcome the major hurdle of “mispairing” in TCR gene therapy.

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Section: Discussionmentioning

confidence: 88%

Engineering antigen‐specific NK cell lines against the melanoma‐associated antigen tyrosinase via TCR gene transfer

et al. 2019

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“…63 Another well-studied costimulatory adhesion molecule, CD226 (DNAM-1), which is involved in synapse formation and NK-mediated cytotoxicity of certain tumors, co-localizes with LFA-1 and facilitates LFA-1 mediated contacts. 64 The synergy between CD226 and LFA-1 in educated NK cells constitutes an important regulator in cell conjugation formation and promotion of NK cell reactivity. 65 Moreover, the expression pattern of CD226 is correlated with that of MHC-I-specific inhibitory receptors, suggesting that CD226 acts as a sensor of classical NK cell education.…”

Section: Signals Of Nk Cell Educationmentioning

confidence: 99%

NK cell education via nonclassical MHC and non-MHC ligands

2016

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Natural killer (NK) cell education, a process for achieving functional maturation and self-tolerance, has been previously defined by the interaction between self-major histocompatibility complex class I (MHC-I) molecules and their specific inhibitory receptors. Over the past several years, growing evidence has highlighted the important roles of nonclassical MHC-I and non-MHC-I molecules in NK cell education. Herein, we review the current knowledge of NK cell education, with a particular focus on nonclassical MHC-I- and non-MHC-I-dependent education, and compare them with the classical MHC-I-dependent education theory. In addition, we update and extend this theory by presenting the 'Confining Model', discussing cis and trans characteristics, reassessing quantity and quality control, and elucidating the redundancy of NK cell education in tumor and virus infection.

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“…Furthermore, because many tumor types overexpress PVR (17)(18)(19)(20), differential expression of DNAM-1 in NK cells may also be critically involved in regulating the function of educated NK cells during the effector phase. .…”

Section: Dnam-1 Is An Intrinsic Marker Of Nk Cell Educationmentioning

confidence: 99%

“…Thus, DNAM-1 could serve as an important link between lymphocyte activation and the downstream engagement in functional immune synapses with target cells. In favor of this notion, DNAM-1 facilitates LFA-1-mediated T cell costimulation (17) and promotes the formation of stable target cell conjugates (18,19). Similarly, triggering of DNAM-1 on human NK cells induces inside-out signals for LFA-1 (20), thus boosting conjugate formation.…”

mentioning

confidence: 99%

Coordinated Expression of DNAM-1 and LFA-1 in Educated NK Cells

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Forslund

et al. 2015

The Journal of Immunology

106

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The functional capacity of NK cells is dynamically tuned by integrated signals from inhibitory and activating cell surface receptors in a process termed NK cell education. However, the understanding of the cellular and molecular mechanisms behind this functional tuning is limited. In this study, we show that the expression of the adhesion molecule and activation receptor DNAX accessory molecule 1 (DNAM-1) correlates with the quantity and quality of the inhibitory input by HLA class I–specific killer cell Ig-like receptors and CD94/NKG2A as well as with the magnitude of functional responses. Upon target cell recognition, the conformational state of LFA-1 changed in educated NK cells, associated with rapid colocalization of both active LFA-1 and DNAM-1 at the immune synapse. Thus, the coordinated expression of LFA-1 and DNAM-1 is a central component of NK cell education and provides a potential mechanism for controlling cytotoxicity by functionally mature NK cells.

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CD226 Protein Is Involved in Immune Synapse Formation and Triggers Natural Killer (NK) Cell Activation via Its First Extracellular Domain

Cited by 28 publications

References 37 publications

Engineering antigen‐specific NK cell lines against the melanoma‐associated antigen tyrosinase via TCR gene transfer

Engineering antigen‐specific NK cell lines against the melanoma‐associated antigen tyrosinase via TCR gene transfer

NK cell education via nonclassical MHC and non-MHC ligands

Coordinated Expression of DNAM-1 and LFA-1 in Educated NK Cells

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