Open AccessIdentification of TAPBPL as a novel negative regulator of T‐cell function
Author(s) -
Lin Yujun,
Cui Cheng,
Su Min,
Silbart Lawrence K,
Liu Haiyan,
Zhao Jin,
He Lang,
Huang Yuanmao,
Xu Dexin,
Wei Xiaodan,
Du Qian,
Lai Laijun
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202013404
Subject(s) - biology , immune system , t cell , experimental autoimmune encephalomyelitis , cd8 , fusion protein , monoclonal antibody , cytokine , microbiology and biotechnology , cytotoxic t cell , antibody , in vitro , immunology , recombinant dna , biochemistry , gene
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.