Identification of CD112R as a novel checkpoint for human T cells

J Exp Med. 2016 Feb 8;213(2):167-76. doi: 10.1084/jem.20150785. Epub 2016 Jan 11.

Abstract

T cell immunoglobulin and ITIM domain (TIGIT) and CD226 emerge as a novel T cell cosignaling pathway in which CD226 and TIGIT serve as costimulatory and coinhibitory receptors, respectively, for the ligands CD155 and CD112. In this study, we describe CD112R, a member of poliovirus receptor-like proteins, as a new coinhibitory receptor for human T cells. CD112R is preferentially expressed on T cells and inhibits T cell receptor-mediated signals. We further identify that CD112, widely expressed on antigen-presenting cells and tumor cells, is the ligand for CD112R with high affinity. CD112R competes with CD226 to bind to CD112. Disrupting the CD112R-CD112 interaction enhances human T cell response. Our experiments identify CD112R as a novel checkpoint for human T cells via interaction with CD112.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / immunology*
  • Cell Adhesion Molecules / metabolism
  • Cell Cycle Checkpoints / immunology
  • Cell Line, Tumor
  • Dendritic Cells / immunology
  • HEK293 Cells
  • Humans
  • Interleukin-2 Receptor beta Subunit / metabolism*
  • Ligands
  • Lymphocyte Activation
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Nectins
  • Phylogeny
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Receptors, Cell Surface / metabolism
  • Receptors, Virus / genetics
  • Receptors, Virus / immunology
  • Receptors, Virus / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Cell Adhesion Molecules
  • IL2RB protein, human
  • Interleukin-2 Receptor beta Subunit
  • Ligands
  • Nectins
  • PVRIG protein, human
  • Receptors, Antigen, T-Cell
  • Receptors, Cell Surface
  • Receptors, Virus
  • Recombinant Fusion Proteins
  • poliovirus receptor

Associated data

  • GENBANK/BC073861
  • PDB/4JJH
  • RefSeq/.1
  • RefSeq/XM_011240964