1. Academic Validation
  2. Identification of CD112R as a novel checkpoint for human T cells

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.
Yuwen Zhu 1 Alessandro Paniccia 2 Alexander C Schulick 2 Wei Chen 3 Michelle R Koenig 2 Joshua T Byers 2 Sheng Yao 4 Shaun Bevers 5 Barish H Edil 1
Affiliations

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.

Figures