Identification of TAPBPL as a novel negative regulator of T-cell function.
EMBO Mol Med
; 13(5): e13404, 2021 05 07.
Article
em En
| MEDLINE
| ID: mdl-33938620
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD8-Positivos
/
Encefalomielite Autoimune Experimental
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
EMBO Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos