title: Identification of CD112R as a novel checkpoint for human T cells.
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.
authors.affiliation: Department of Surgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045 yuwen.zhu@ucdenver.edu barish.edil@ucdenver.edu.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Surgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Paniccia
authors.affiliation: Department of Surgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Schulick
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Surgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Koenig
authors.affiliation: Department of Surgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Byers
authors.affiliation: TopAlliance Biosciences, Inc., Rockville, MD 20850.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Biochemistry and Molecular Genetics, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045.
authors.forename: Shaun
authors.initials: S
authors.lastname: Bevers
authors.affiliation: Department of Surgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045 yuwen.zhu@ucdenver.edu barish.edil@ucdenver.edu.
authors.forename: Barish H
authors.initials: BH
authors.lastname: Edil
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D053646:Interleukin-2 Receptor beta Subunit / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000075983:Nectins; D010802:Phylogeny; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D015815:Cell Adhesion Molecules; C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; D008024:Ligands; D000075983:Nectins; C000609742:PVRIG protein, human; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C066100:poliovirus receptor