The Pekin duck programmed death‐ligand 1: cDNA cloning, genomic structure, molecular characterization and mRNA expression analysis

Abstract

Programmed death ligand-1 (PD-L1) plays an important role in the attenuation of adaptive immune responses in higher vertebrates. Here, we describe the identification of the Pekin duck PD-L1 orthologue (duPD-L1) and its gene structure. The duPD-L1 cDNA encodes a 311-amino acid protein that has an amino acid identity of 78% and 42% with chicken and human PD-L1, respectively. Mapping of the duPD-L1 cDNA with duck genomic sequences revealed an exonic structure of its coding sequence similar to those of other vertebrates but lacked a noncoding exon 1. Homology modelling of the duPD-L1 extracellular domain was compatible with the tandem IgV-like and IgC-like IgSF domain structure of human PD-L1 (PDB ID: 3BIS). Residues known to be important for receptor binding of human PD-L1 were mostly conserved in duPD-L1 within the N-terminus and the G sheet, and partially conserved within the F sheet but not within sheets C and C'. DuPD-L1 mRNA was constitutively expressed in all tissues examined with highest expression levels in lung and spleen and very low levels of expression in muscle, kidney and brain. Mitogen stimulation of duck peripheral blood mononuclear cells transiently increased duPD-L1 mRNA expression. Our observations demonstrate evolutionary conservation of the exonic structure of its coding sequence, the extracellular domain structure and residues implicated in receptor binding, but the role of the longer cytoplasmic tail in avian PD-L1 proteins remains to be determined.

Inhibitors of the PD-1/PD-L1 axis for the treatment of head and neck cancer: current status and future perspectives

“…The PD-1 ligands termed PD-L1 and PD-L2 belong to the B7 superfamily, and the family members also include B7-1 (cluster of differentiation [CD]80), B7-2 (CD86), B7-H2, B7-H3, B7-H4, and B7-H6 14,23. The structures of PD-L1 and PD-L2 mainly comprise an extracellular region consisting of IgV-like structures in series and immunoglobulin constant region-like structures, a hydrophobic transmembrane region, and an intracellular region with a short cytoplasmic tail of unknown function 20,23.…”

“…The structures of PD-L1 and PD-L2 mainly comprise an extracellular region consisting of IgV-like structures in series and immunoglobulin constant region-like structures, a hydrophobic transmembrane region, and an intracellular region with a short cytoplasmic tail of unknown function 20,23. The affinity of the PD-L1 extracellular region with PD-1 is lower than that of the PD-L2 extracellular region with PD-1.…”

“…The affinity of the PD-L1 extracellular region with PD-1 is lower than that of the PD-L2 extracellular region with PD-1. However, the PD-L1 extracellular region can also bind with the B7-A (CD80) extracellular region 14,20,23. PD-L2 is expressed only in activated macrophages and dendrites;20 hence, only few studies have been done on PD-L2.…”

Immune checkpoint blockade therapy in head and neck cancer: a review

“…PD-1 is a member of the CD28/CTLA-4/ICOS costimulatory receptor family type-I transmembrane glycoprotein, mainly comprises an extracellular region, a hydrophobic transmembrane region, and an intracellular tyrosine residue containing region [14][15][16][17] . The PD-1 receptor binds to its ligands PDL-1/2, presence in tumor cells, thus mediated inhibitory signal to the T-cells ( Figure:2 a).…”

“…PDL-1 is expressed constitutively at low levels on antigen-presenting cells (APCs) and a wide variety of non-hematopoietic cell types 14,20,24 . Inflammatory cytokines such as type I and type II interferons as well as TNF-α (tumor necrosis factor α) and oncogenic VEGF (vascular endothelial growth factor) can induce PDL-1 expression 14,17 . On the other hand, tumor cell upregulates PDL-1 expression mainly via four mechanisms and tumor cell-derived cytokine also can unregulated PDL-1 expression ( Figure:3).…”