Disease relevance of LAG3

• Association analysis of the LAG3 and CD4 genes in multiple sclerosis in two independent populations [1].
• In contrast to CD4, LAG-3 does not bind the human immunodeficiency virus gp120 [2].
• The reactivity of these reagents is directed against LAG-3 since they recognize both membrane-expressed and soluble recombinant LAG-3 molecules produced in a baculovirus expression system [2].
• Nonrheumatoid IgM in human hepatitis C virus-associated type II cryoglobulinemia recognize mimotopes of the CD4-like LAG-3 protein [3].
• Immunohistochemical analysis confirmed LAG-3 expression by TILs in 9/11 RCCs, as well as in tumours of different origins, such as melanomas (3/5) and lymphomas (7/7) [4].

High impact information on LAG3

• Here we identify LAG-3, a glutamine-rich protein that forms a ternary complex together with the LAG-1 DNA-binding protein and the receptor's intracellular domain [5].
• Using RNA interference, we find that LAG-3 activity is crucial in Caenorhabditis elegans for both GLP-1 and LIN-12 signalling [5].
• The two antibodies are likely to react with the same or closely related epitope (termed LAG-3.1) exposed on the LAG-3 first domain extra loop, as assessed in competition experiments on LAG-3-expressing activated lymphocytes [2].
• The lymphocyte activation gene 3 (LAG-3), expressed in human activated T and natural killer (NK) cells, is closely related to CD4 at the gene and protein levels [2].
• Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens [2].

Biological context of LAG3

• Characterization of the major histocompatibility complex class II binding site on LAG-3 protein [6].
• Nothing is known about the LAG-3 regions or residues required to form a stable MHC class II binding site [6].
• The binding of Ab to the LAG-3 molecule followed by cross-linking (XL) inhibits cell proliferation and cytokine secretion in response to CD3XL on activated T cells [7].
• LAP, a lymphocyte activation gene-3 (LAG-3)-associated protein that binds to a repeated EP motif in the intracellular region of LAG-3, may participate in the down-regulation of the CD3/TCR activation pathway [8].
• After additional genotyping in stage two, two genes--each containing at least three significantly (P<0.05) associated SNPs--conferred susceptibility to MS: LAG3 on chromosome 12p13, and IL7R on 5p13 [9].

Anatomical context of LAG3

• Maturation and activation of dendritic cells induced by lymphocyte activation gene-3 (CD223) [10].
• Lymphocyte activation gene-3 (LAG-3) is an MHC class II ligand expressed on activated T and NK cells [10].
• They ultimately suggest that LAG-3 is an inhibitory receptor in activated T lymphocytes [7].
• We investigated whether LAG-3 could be used in vivo to stimulate MHC class II(+) antigen-presenting cells (APC), such as resident macrophages or dendritic cells known to play a crucial role in processing and presenting of antigens to the immune system [11].
• LAG3 inhibits activated T cells, while IL7R is necessary for the maturation of T and B cells [9].

Associations of LAG3 with chemical compounds

• We first investigated whether LAG-3 is localized in activated T cells in detergent-resistant membrane rafts enriched in glycosphingolipids and cholesterol [8].
• Engagement of class II molecules by both its natural ligand LAG-3 and class II mAb induces rapid protein phosphorylation of phospholipase Cgamma2 (PLCgamma2) and p72syk as well as activation of phosphatidyl inositol 3-kinase/Akt, p42/44 extracellular signal-regulated protein kinase, and p38 mitogen-activated protein kinase pathways [12].

Regulatory relationships of LAG3

• Indeed, anti-LAG-3 mAb inhibits both IL-12 and IFN-gamma production in IL-2-stimulated cocultures of T cells and autologous monocytes [13].

Other interactions of LAG3

• Molecular cloning, characterisation and tissue-specific expression of human LAG3, a member of the novel Lag1 protein family [14].
• The lymphocyte activation gene-3 (LAG-3) molecule is a T cell activation Ag closely related to CD4 at the gene and protein levels [7].
• Using the LAG-3 intracytoplasmic region as bait in the yeast two-hybrid cloning system, we next identified a novel protein termed LAP for LAG-3-associated protein [8].
• The MHC class II ligand lymphocyte activation gene-3 is co-distributed with CD8 and CD3-TCR molecules after their engagement by mAb or peptide-MHC class I complexes [15].
• The lymphocyte activation gene product (LAG-3), a ligand for MHC class II molecules co-caps with the CD3/TCR complex and inhibits cell proliferation and cytokine secretion in response to CD3 signaling [8].

Analytical, diagnostic and therapeutic context of LAG3

• In Western blot analysis, only the former molecule was recognized by the anti-LAG-3 antibodies, demonstrating that it is LAG-3 encoded [2].
• We first show that areas of raft aggregation (both cholesterol rich and CDw78 microdomains) could be visualized using a soluble LAG-3 protein and confocal microscopy [12].
• IgM purified from CryoII/HCV patients' sera specifically reacted with the LAG-3 peptide in ELISA, and this binding was inhibited by the selected phagotopes [3].
• LAG-3: a regulator of T-cell and DC responses and its use in therapeutic vaccination [16].

References