PD-L2 is a second ligand for PD-1 and inhibits T cell activation

Nat Immunol. 2001 Mar;2(3):261-8. doi: 10.1038/85330.

Abstract

Programmed death I (PD-I)-deficient mice develop a variety of autoimmune-like diseases, which suggests that this immunoinhibitory receptor plays an important role in tolerance. We identify here PD-1 ligand 2 (PD-L2) as a second ligand for PD-1 and compare the function and expression of PD-L1 and PD-L2. Engagement of PD-1 by PD-L2 dramatically inhibits T cell receptor (TCR)-mediated proliferation and cytokine production by CD4+ T cells. At low antigen concentrations, PD-L2-PD-1 interactions inhibit strong B7-CD28 signals. In contrast, at high antigen concentrations, PD-L2-PD-1 interactions reduce cytokine production but do not inhibit T cell proliferation. PD-L-PD-1 interactions lead to cell cycle arrest in G0/G1 but do not increase cell death. In addition, ligation of PD-1 + TCR leads to rapid phosphorylation of SHP-2, as compared to TCR ligation alone. PD-L expression was up-regulated on antigen-presenting cells by interferon gamma treatment and was also present on some normal tissues and tumor cell lines. Taken together, these studies show overlapping functions of PD-L1 and PD-L2 and indicate a key role for the PD-L-PD-1 pathway in regulatingT cell responses.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Antigens, Surface / immunology*
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen*
  • B7-H1 Antigen
  • Blood Proteins*
  • CD28 Antigens / immunology
  • CHO Cells
  • Cells, Cultured
  • Cricetinae
  • Cytokines / biosynthesis
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Jurkat Cells
  • Ligands
  • Lymphocyte Activation*
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Peptides / genetics
  • Peptides / immunology*
  • Peptides / metabolism
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell / immunology
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / immunology*
  • Transfection

Substances

  • Antigens, CD
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen
  • B7-H1 Antigen
  • Blood Proteins
  • CD274 protein, human
  • CD28 Antigens
  • Cd274 protein, mouse
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Glycoproteins
  • PDCD1 protein, human
  • PDCD1LG2 protein, human
  • Pdcd1 protein, mouse
  • Pdcd1lg2 protein, mouse
  • Peptides
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell

Associated data

  • GENBANK/AF142780
  • GENBANK/AF344424