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

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.

Pubmed ID: 11224527


  • Latchman Y
  • Wood CR
  • Chernova T
  • Chaudhary D
  • Borde M
  • Chernova I
  • Iwai Y
  • Long AJ
  • Brown JA
  • Nunes R
  • Greenfield EA
  • Bourque K
  • Boussiotis VA
  • Carter LL
  • Carreno BM
  • Malenkovich N
  • Nishimura H
  • Okazaki T
  • Honjo T
  • Sharpe AH
  • Freeman GJ


Nature immunology

Publication Data

March 26, 2001

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI38310
  • Agency: NIAID NIH HHS, Id: AI39671
  • Agency: NIAID NIH HHS, Id: AI40614

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Antigens, CD274
  • Antigens, CD28
  • Antigens, CD80
  • Antigens, Surface
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Blood Proteins
  • CHO Cells
  • Cells, Cultured
  • Cricetinae
  • Cytokines
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Jurkat Cells
  • Ligands
  • Lymphocyte Activation
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Peptides
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell
  • Sequence Homology, Amino Acid
  • T-Lymphocytes
  • Transfection