Author Correction: A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals

Demetriou, Philippos; Abu-Shah, Enas; Valvo, Salvatore; McCuaig, Sarah; Mayya, Viveka; Kvalvaag, Audun; Starkey, Thomas; Korobchevskaya, Kseniya; L, Lee; Friedrich, Matthias; Mann, Edward O.; Kutuzov, Mikhail A.; Morotti, Matteo; Wietek, Nina; Rada, Heather; Yusuf, Salim; Afrose, Jehan; Siokis, Anastasios; Meyer‐Hermann, Michael; Ahmed, Ambar; Depoil, David; Dustin, Michael L.

doi:10.1038/s41590-020-00825-w

Cited by 17 publications

(27 citation statements)

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“…In humans, CD2 interacts with CD58, which, like mouse CD48, is GPI-linked and expressed not only on APCs but also on T cells (6,8). Although human CD2 can interact with human CD48, this interaction was described to be of much lower affinity (22).…”

Section: Cis Interactions Of Cd2 and Cd58 Promote Human T Cell Activa...mentioning

confidence: 99%

“…CD58 is highly expressed in effectormemory and innate-like T cells in humans, in amounts also analogous to those seen in APCs (www.immgen.org/Databrowser19/Human-ExpressionData.html). Imaging analyses using CD58 immobilized on artificial lipid bilayers suggested that, upon engagement by ligands on APCs (hereafter termed "trans" interactions), CD2 becomes part of the T cell "immunological synapse" (8)(9)(10). As stimulation of T cells with agonistic anti-CD2 antibodies (Abs) resulted in markedly enhanced T cell activation, it has been implied that CD2 is a potent T cell-activating receptor (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

“…Although CD2 has been presumed to be engaged by ligands displayed on APCs (8,9), these ligands are also expressed on T cells, suggesting that interactions within individual T cells or between adjacent T cells (hereafter termed "cis T " and "cis T-T " interactions, respectively) may also exist. Some evidence in support of this idea was reported by others (4,16,17), although the prevalent view is still that CD2 is engaged by ligands from APCs.…”

Section: Introductionmentioning

confidence: 99%

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Cis interactions between CD2 and its ligands on T cells are required for T cell activation

Zhong

et al. 2022

Sci. Immunol.

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CD2 is largely described to promote T cell activation when engaged by its ligands, CD48 in mice and CD58 in humans, that are present on antigen-presenting cells (APCs). However, both CD48 and CD58 are also expressed on T cells. By generating new knockout mouse strains lacking CD2 or CD48 in the C57BL/6 background, we determined that whereas CD2 was necessary on T cells for T cell activation, its ligand CD48 was not required on APCs. Rather, CD48 was also needed on T cells. One exception was during cytotoxicity, which required CD48 on T cells and APCs. Fluorescence resonance energy transfer (FRET) studies in nonimmune cells provided evidence that cis interactions between CD2 and CD48 existed within individual cells. CD2-CD48 interactions on T cells enabled more robust T cell receptor (TCR) signals, including protein tyrosine phosphorylation. Using T cells from a CD2 knock-in mouse in which a tag was inserted at the carboxyl terminus of CD2, mass spectrometry analyses revealed that the role of CD2 in T cell activation correlated with its ability to interact with components of the TCR complex and the protein tyrosine kinase Lck. CD2-CD58 provided a similar function in human T cells. Thus, our data imply that T cell–intrinsic cis interactions of CD2 with its ligands are required for TCR signaling and T cell activation. Interactions with ligands on APCs contribute during cytotoxicity.

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Section: Cis Interactions Of Cd2 and Cd58 Promote Human T Cell Activa...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cis interactions between CD2 and its ligands on T cells are required for T cell activation

Zhong

et al. 2022

Sci. Immunol.

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“…[ 8,38,48 ] Moreover, a recent study by Demetriou et al has shown that CD2 interaction with its ligand CD58 induces reorganization of several co‐stimulatory receptor‐ligand pairs, including CD28, to the periphery of the supramolecular activation complex (SMAC). [ 49 ] Furthermore, distal CD28 signaling has been shown to induce enhanced IL‐2 production in naïve CD4 + T cells. [ 50 ] Co‐presentation of both these mAbs could therefore allow for synergistic T‐cell activation by targeting not only these distinct pathways but also induce a more potent SMAC organization.…”

Section: Discussionmentioning

confidence: 99%

Dictating Phenotype, Function, and Fate of Human T Cells with Co‐Stimulatory Antibodies Presented by Filamentous Immune Cell Mimics

Schluck

Eggermont

Weiden

et al. 2022

Advanced Therapeutics

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T cells require a co‐stimulatory signal in addition to T‐cell receptor (TCR) stimulation to achieve full activation. While most studies focus on the co‐stimulatory receptor CD28, little is known about the role of the other co‐stimulatory receptors in T‐cell signaling. A deeper understanding of how co‐stimulatory receptor signaling cooperates with TCR signaling could improve the ability to control T‐cell function and benefit the design of T‐cell based immunotherapies. Artificial antigen presenting cells (aAPCs) enable tight control over the signals given to T cells. In this study, filamentous polyisocyanopeptide (PIC) polymers (immunofilaments) are used as nanosized aAPCs to study the role of the engagement of six distinct co‐stimulatory molecules on human T‐cell phenotype, function, and fate in the context of TCR signaling. The immunofilaments highlight important roles for CD28 and CD2 signaling in T‐cell priming, proliferation, cytokine production, and multifunctionality. Taken together, this work provides insight into the role of combined TCR and co‐stimulation on T‐cell phenotype, function, and fate using immunofilaments. Notably, the findings on the roles of co‐stimulatory molecule function can be used for the rational design of future cancer immunotherapies.

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“…The interaction between CD2 and CD58 is known to play a critical role in the formation of a productive immunological synapse [22][23][24] . We found that the inhibition of this interaction with an anti-CD2 blocking antibody partially reversed the cytotoxicity enhancement from the sialidase addition, further suggesting that the desialylation triggers stronger target cell killing by facilitating a tighter interaction between target tumor cells and T cells (Figure 2e).…”

Section: Tumor Cell Desialylation Promotes Stronger Bite-mediated Imm...mentioning

confidence: 99%

Enhancing the anti-tumor efficacy of Bispecific T cell engagers via cell surface glycocalyx editing

Yang

Grande

Hou

et al. 2022

Preprint

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Bispecific T cell engager (BiTE)-based cancer therapies that activate the cytotoxic T cells of a patient's own immune system have gained momentum with the recent FDA approval of Blinatumomab for treating B cell malignancies. However, this approach has had limited success in targeting solid tumors. Here, we report the development of BiTE-sialidase fusion proteins that enhance tumor cell susceptibility to BiTE-mediated cytolysis by T cells via selective desialylation at the T cell-tumor cell interface that results in better immunological synapse formation. We show that a BiTE-sialidase fusion protein targeting human epidermal growth factor receptor 2 (HER2) exhibits remarkably increased efficacy in terms of killing HER2 positive tumor cells when compared to the BiTE alone. This enhanced function is seen both in vitro and in an in vivo xenograft solid tumor model. We feel that BiTE-sialidase fusion proteins have great potential as candidates for the development of next generation bispecific T-cell engaging molecules for cancer immunotherapy.

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Author Correction: A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals

Cited by 17 publications

References 0 publications

Cis interactions between CD2 and its ligands on T cells are required for T cell activation

Cis interactions between CD2 and its ligands on T cells are required for T cell activation

Dictating Phenotype, Function, and Fate of Human T Cells with Co‐Stimulatory Antibodies Presented by Filamentous Immune Cell Mimics

Enhancing the anti-tumor efficacy of Bispecific T cell engagers via cell surface glycocalyx editing

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