Identification of TAPBPL as a novel negative regulator of T‐cell function
Open Access
- 3 May 2021
- journal article
- research article
- Published by EMBO in EMBO Molecular Medicine
- Vol. 13 (5), e13404
- https://doi.org/10.15252/emmm.202013404
Abstract
T cell stimulatory and inhibitory molecules are critical for the regulation of immune responses. In this study, we identify a novel T cell co‐inhibitory molecule TAPBPL, whose amino acid sequence shares homology with known B7 family members. TAPBPL protein is expressed on resting and activated T cells, B cells, monocytes, and dendritic cells (DCs), as well as on some tumor tissues. The putative TAPBPL receptor is expressed on activated CD4 and CD8 T cells. A soluble recombinant human TAPBPL‐IgG Fc (hTAPBPL‐Ig) fusion protein inhibits the proliferation, activation, and cytokine production of both mouse and human T cells in vitro. In vivo administration of hTAPBPL‐Ig protein attenuates experimental autoimmune encephalomyelitis (EAE) in mice. Furthermore, an anti‐TAPBPL monoclonal antibody neutralizes the inhibitory activity of hTAPBPL‐Ig on T cells, enhances antitumor immunity, and inhibits tumor growth in animal models. Our results suggest that therapeutic intervention of the TAPBPL inhibitory pathway may represent a new strategy to modulate T cell‐mediated immunity for the treatment of cancer, infections, autoimmune diseases, and transplant rejection.Funding Information
- National Institute of Allergy and Infectious Diseases (1R01AI123131)
- Connecticut Innovations (16‐RMB‐UCONN‐02)
This publication has 35 references indexed in Scilit:
- Recombinant IL-7/HGFβ efficiently induces transplantable murine hematopoietic stem cellsJCI Insight, 2012
- Selective Effects of PD-1 on Akt and Ras Pathways Regulate Molecular Components of the Cell Cycle and Inhibit T Cell ProliferationScience Signaling, 2012
- B7-H4 Treatment of T Cells Inhibits ERK, JNK, p38, and AKT ActivationPLOS ONE, 2012
- In Vivo Administration of the Recombinant IL-7/Hepatocyte Growth Factor β Hybrid Cytokine Efficiently Restores Thymopoiesis and Naive T Cell Generation in Lethally Irradiated Mice after Syngeneic Bone Marrow TransplantationThe Journal of Immunology, 2011
- The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humansThe Journal of Experimental Medicine, 2009
- Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte ActivationThe Journal of Experimental Medicine, 2000
- B7h, a Novel Costimulatory Homolog of B7.1 and B7.2, Is Induced by TNFαImmunity, 1999
- Mitogen-activated protein kinase cascades and regulation of gene expressionCurrent Opinion in Immunology, 1996
- Cloning of B7-2: a CTLA-4 Counter-Receptor That Costimulates Human T Cell ProliferationScience, 1993
- Structure, expression, and T cell costimulatory activity of the murine homologue of the human B lymphocyte activation antigen B7.The Journal of Experimental Medicine, 1991