Identification of CD112R as a novel checkpoint for human T cells

Yuwen Zhu; Alessandro Paniccia; Alexander C Schulick; Wei Chen; Michelle R Koenig; Joshua T Byers; Sheng Yao; Shaun Bevers; Barish H Edil

doi:10.1084/jem.20150785

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.

Authors

Yuwen Zhu¹, Alessandro Paniccia², Alexander C Schulick², Wei Chen³, Michelle R Koenig², Joshua T Byers², Sheng Yao⁴, Shaun Bevers⁵, Barish H Edil¹

Affiliations

¹ Department of Surgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045 [email protected] [email protected].
² Department of Surgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045.
³ Department of Surgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045 Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University, 310027 Hangzhou, China.
⁴ TopAlliance Biosciences, Inc., Rockville, MD 20850.
⁵ Department of Biochemistry and Molecular Genetics, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045.

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