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.
Mesh Terms:
Amino Acid Sequence, Animals, Antigens, CD, 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, Receptors, Antigen, T-Cell, Sequence Homology, Amino Acid, T-Lymphocytes, Transfection
Nat. Immunol.
Date: Mar. 01, 2001
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