Showing papers by "Clive Wood published in 2001"

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

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.

Pd-l2 molecules: novel pd-1 ligands and uses therefor

Abstract: The invention provides isolated nucleic acids molecules, designated PD-L2 nucleic acid molecules, which encode novel B7-related molecules which are ligands for PD-1. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PD-L2 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PD-L2 gene has been introduced or disrupted. The invention further provides isolated PD-L2 polypeptides, fusion proteins, antigenic peptides and anti-PD-L2 antibodies. The invention still further provides methods for promoting or inhibiting the interaction between PD-L2 and PD-1. Diagnostic and treatment methods utilizing compositions of the invention are also provided.

Antibodies against CTLA4

Abstract: The invention provides an antibody-toxic moiety conjugates comprising an antibody that specifically recognizes a molecule expressed on the surface of a T cell which is expressed only on T cells and is only expressed transiently on T cells upon T cell activation. Preferably, the T cell molecule is CTLA4. The invention further provides anti-CTLA4 antibodies and humanized forms thereof.

Pd-l2 molecules: pd-1 ligands and uses therefor

Abstract: The invention provides isolated nucleic acid molecules, designated PD-L2 nucleic acid molecules, which encode novel B7-related molecules which are ligands for PD-1. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PD-L2 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PD-L2 gene has been introduced or disrupted. The invention further provides isolated PD-L2 polypeptides, fusion proteins, antigenic peptides and anti-PD-L2 antibodies. The invention still further provides methods for promoting or inhibiting the interaction between PD-L2 and PD-1. Diagnostic and treatment methods utilizing compositions of the invention are also provided.

Antibodies against ctla4(cd152), conjugates comprising same, and uses thereof

Abstract: The invention provides an antibody- toxic moiety conjugates comprising an antibody that specifically recognizes a molecule expressed on the surface of a T cell which is expressed only on T cells and is only expressed transiently on T cells upon T cell activation. Preferably, the T cell molecule is CTLA4. The invention further provides anti-CTLA4 antibodies and humanized forms thereof.

Trade molecules and uses related thereto

Abstract: The present invention relates, at least in part, to methods of modulating proliferation and apoptotic state of cells using agents that modulate the expression and/or activity of TRADE family polypeptides. In addition, the invention provides two novel members of the TRADE family of molecules.

Methods of identifying compounds that upmodulate T cell activation in the presence of a PD-1 mediated signal

Abstract: The invention provides isolated nucleic acids molecules, designated PD-L2 nucleic acid molecules, which encode novel B7-related molecules which are ligands for PD-1. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PD-L2 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PD-L2 gene has been introduced or disrupted. The invention further provides isolated PD-L2 polypeptides, fusion proteins, antigenic peptides and anti-PD-L2 antibodies. The invention still further provides methods for promoting or inhibiting the interaction between PD-L2 and PD-1. The invention further provides methods of identifying compounds that upmodulate T cell activation in the presence of a PD-1-mediated signal. Diagnostic and treatment methods utilizing compositions of the invention are also provided.

Molecules pd-l2 : nouveaux ligands de pd-1 et utilisations de ceux-ci

Abstract: L'invention concerne des molecules d'acides nucleiques isolees appelees molecules d'acides nucleiques PD-L2, codant de nouvelles molecules associees a B7, ces dernieres molecules etant des ligands de PD-1. L'invention concerne egalement des molecules d'acides nucleiques antisens, des vecteurs d'expression de recombinaison contenant des molecules d'acides nucleiques PD-L2, des cellules hotes dans lesquelles les vecteurs d'expression ont ete introduits, ainsi que des animaux transgeniques non-humains dans lesquels une gene PD-L2 a ete introduit ou interrompu. L'invention concerne egalement des polypeptides PD-L2 isoles, des proteines de fusion, des peptides antigenes, et des anticorps anti-PD-L2. L'invention concerne egalement des procedes destines a favoriser ou inhiber l'interaction entre PD-L2 et PD-1. L'invention concerne egalement des procedes de diagnostic et de traitement faisant intervenir des compositions selon l'invention.

Molecules trade et utilisations associees a ces dernieres

Abstract: L'invention concerne, en partie au moins, des procedes permettant de moduler la proliferation de l'etat apoptotique de cellules, qui reposent sur l'utilisation d'agents qui modulent l'expression et/ou l'activite de polypeptides de la famille TRADE. L'invention concerne, par ailleurs, deux nouveaux membres de la famille de molecules TRADE.

Use of the extracellular domain of TRADE molecules in medicaments for treating neoplasia

Abstract: The present invention relates, at least in part, to methods of modulating proliferation and apoptotic state of cells using agents that modulate the expression and/or activity of TRADE family polypeptides. In addition, the invention provides two novel members of the TRADE family of molecules.