The poliovirus receptor (PVR)-like molecules are a newly emerging group of the immunoglobulin superfamily (IgSF) that play important regulatory roles in NK cell functions. These surface molecules share PVR signature motifs in the first immunoglobulin variable-like (IgV) domain and are originally known to mediate epithelial cell-cell contact. CD112 (also known as PVRL2 or Nectin-2) is one of the major ligands heavily expressed on many cancer cells. It interacts with CD226 (DNAM-1) to stimulate T and NK cells. CD122 also inhibits T/NK cell functions through another coinhibitory receptor, T cell immunoglobulin and ITIM domain (TIGIT).
Fig.1 In healthy cells, limiting CD112 membrane expression may avoid a potential aberrant NK cell activation. (Molfetta, 2019)
CD112R is a new inhibitory receptor of the PVR-like family, which interacts with CD112. CD112R is expressed on human NK cells, though its function on this cell type is unclear. CD112R contains an extracellular Ig-like domain, a transmembrane sequence, and a cytoplasmic tail with two tyrosine phosphorylation sites, including an ITIM-like motif. The binding of CD112R to its ligand recruits SHP1 and SHP2 that trigger the TCR/CD28 signaling inhibition in T cells.
Overview of CD112R and CD112 Pathway
The CD112 and CD112R pathway has not been thoroughly studied. Researchers have demonstrated some of the phenomena of the interaction of CD112 and CD112R pathway on cells; however, the mechanism studies are still on the way. Judging from the results of the research so far, CD112R protein binds to many cell types, including DCs and human cancer cells. CD112 on DCs mediated the CD112R interaction. Collectively, CD112 is the main ligand, if not the only one, that mediates the interaction of CD112R with DCs and tumor cells. In addition, although the mechanism has not been clarified, the interaction of CD112 and CD112R can inhibit T cell proliferation.
Services at Creative Biolabs
Creative Biolabs is an industry-leading immune checkpoint-related service provider. We have an advanced technology platform and extensive experience to provide a series of customer services for the CD112R and CD112 pathway, including but not limited to: