The N-linked glycosylations of TIGIT Asn32 and Asn101 facilitate PVR/TIGIT interaction

Biochem Biophys Res Commun. 2021 Jul 12:562:9-14. doi: 10.1016/j.bbrc.2021.05.034. Epub 2021 May 21.

Abstract

Although the PVR/TIGIT immune checkpoint axis has been suggested as a promising target for cancer immunotherapy and multiple TIGIT-targeting therapies are undergoing clinical trials, the underlying regulatory mechanisms of PVR/TIGIT interaction remain inconclusive. Here we show that TIGIT N-glycosylations are critical for maintaining the interaction between TIGIT and PVR. TIGIT has two N-glycosylation residues, N32 and N101. N-glycosylation on N101 of TIGIT and, to less extent, on N32, play potent roles in PVR binding. Taken together, these findings suggest that the N-glycosylation sites on TIGIT, especially residue N101, may be potential targets for PVR/TIGIT immune checkpoint blockade.

Keywords: CD155; N-linked glycosylation; PVR; TIGIT; VSTM3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Asparagine / metabolism*
  • Glycosylation
  • HEK293 Cells
  • Humans
  • Protein Binding
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / metabolism*
  • Receptors, Virus / metabolism*

Substances

  • Receptors, Immunologic
  • Receptors, Virus
  • T cell Ig and ITIM domain protein, mouse
  • TIGIT protein, human
  • poliovirus receptor
  • Asparagine