An alternative pathway of T-cell activation: A functional role for the 50 kd T11 sheep erythrocyte receptor protein

Meuer, Stefan; Hussey, Rebecca E.; Fabbi, Marina; Fox, David A.; Acuto, Oreste; Fitzgerald, Kathleen A.; Hodgdon, James C.; Protentis, Jeffrey P.; Schlossman, Stuart F.; Reinherz, Ellis L.

doi:10.1016/0092-8674(84)90039-4

Cited by 1,085 publications

(615 citation statements)

References 31 publications

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“…24 For full activation, however, T cells also require ‘outside-in’ costimulation, which leads to significant rearrangement of the actin cytoskeleton and promotes accumulation of receptors and raft membrane microdomains at the interface between T cells and APCs. 10–12,25 These previous works imply that the artificial engineering of F-actin contents at the IS may mimic the signals evoked by costimulatory molecules. From this perspective, we utilized TAGLN2 as we found in a previous report that TAGLN2 increases F-actin contents through stabilization of F-actin in T cells during IS formation.…”

Section: Discussionmentioning

confidence: 97%

“…9 During IS formation, T-cell antigen receptors (TCRs) constitute the main supramolecular activation clusters (c-SMACs) and elicit the “competence” signal for cellular activation. 8 However, full activation of T cells requires costimulatory “progression” signals resulting from the interaction of accessory receptors, e.g., CD2 10 or CD28, 11,12 with their natural ligands, CD58 or CD80/86, respectively. Interestingly, cumulative evidence has suggested that although TCR stimulation results in actin polymerization, costimulatory signals lead to stronger, large-scale actin responses, which constitute the outermost distal-SMAC (d-SMAC) of the IS and promote the accumulation of receptors to the c-SMAC by retrograde actin flow, thereby resulting in full T-cell activation.…”

Section: Introductionmentioning

confidence: 99%

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Actin stabilizer TAGLN2 potentiates adoptive T cell therapy by boosting the inside-out costimulation via lymphocyte function-associated antigen-1

et al. 2018

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Correct temporal and spatial control of actin dynamics is essential for the cytotoxic T cell effector function against tumor cells. However, little is known whether actin engineering in tumor-targeted T cells can enhance their antitumor responses, thereby potentiating the adoptive T cell therapy. Here, we report that TAGLN2, a 22-KDa actin-stabilizing protein which is physically associated with lymphocyte function-associated antigen-1 (LFA-1), potentiates the OTI TCR CD8+ T cells to kill the intercellular adhesion molecule-1 (ICAM-1)-positive/OVA-presenting E0771 cells, but not ICAM-1-negative OVA-B16F10 cells, suggesting an ‘inside-out’ activation of LFA-1, which causes more efficient immunological synapse formation between T cells and tumor cells. Notably, recombinant TAGLN2 fused with the protein transduction domain (TG2P) overcame the disadvantages of viral gene delivery, leading to a significant reduction in tumor growth in mice. TG2P also potentiated the CD19-targeted, chimeric antigen receptor (CAR)-modified T cells to kill Raji B-lymphoma cells. Our findings indicate that activating the TAGLN2–actin–LFA-1 axis is an effective strategy to potentiate the adoptive T-cell immunotherapy.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Actin stabilizer TAGLN2 potentiates adoptive T cell therapy by boosting the inside-out costimulation via lymphocyte function-associated antigen-1

et al. 2018

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“…Another possibility to be considered is that this mAb recognizes a neoepitope on a surface molecule already expressed by resting cells, which results from conformational changes following activation. Expression of new epitopes after activation have been reported, among others, in CD2, CD45 and α M β 2 integrin [5,10,12].…”

Section: Discussionmentioning

confidence: 99%

Characterization of a novel activation antigen on porcine lymphocytes recognized by monoclonal antibody 5A6/8

Doménech

Bullido²,

Álvarez³

et al. 2004

Vet. Res.

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-In this report, we describe the characterization of a novel activation antigen on porcine lymphocytes recognized by mAb 5A6/8. This antigen was detected on B and T cells 24 h after treatment with various stimuli. It was also found on alveolar macrophages, and at low levels on untreated monocytes. MAb 5A6/8 precipitated two bands of 45 and 50 kDa under non-reducing conditions, and of 22 and 28 kDa under reducing conditions. The cellular distribution, expression kinetics and/or molecular size of the 5A6/8 antigen differ from those of other known lymphocyte activation antigens. MAb 5A6/8 was able to inhibit lymphocyte proliferative responses driven by different stimuli, suggesting a role for this molecule in the events that lead to lymphocyte activation. activation antigen / lymphocyte / monoclonal antibody / monocyte / pig

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“…CD2 + cells routinely exceeded 90% (flow cytometric analysis). Further T-cell enrichment through E-rosetting methods (see [17]) was not performed, to avoid interfering with CD2 antigen which could lead to T-cell activation [20] prior to mitogen treatment. Patch recording was performed on cells with apparent diameter < ~ 8 gin, to minimise the probability of studying macrophages and large granular lymphocytes.…”

Section: Preparation Of Cellsmentioning

confidence: 99%

An electrophysiological study of calcium entry during normal human T‐lymphocyte activation

Ricci

Buffelli

Riviera³

et al. 1996

FEBS Letters

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An alternative pathway of T-cell activation: A functional role for the 50 kd T11 sheep erythrocyte receptor protein

Cited by 1,085 publications

References 31 publications

Actin stabilizer TAGLN2 potentiates adoptive T cell therapy by boosting the inside-out costimulation via lymphocyte function-associated antigen-1

Actin stabilizer TAGLN2 potentiates adoptive T cell therapy by boosting the inside-out costimulation via lymphocyte function-associated antigen-1

Characterization of a novel activation antigen on porcine lymphocytes recognized by monoclonal antibody 5A6/8

An electrophysiological study of calcium entry during normal human T‐lymphocyte activation

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