Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:12209638, PubMed:12421911, PubMed:12672063, PubMed:15100286, PubMed:15634887, PubMed:30580966). Delivers inhibitory signals upon binding to ligands, such as FGL1 (PubMed:30580966). FGL1 constitutes a major ligand of LAG3 and is responsible for LAG3 T-cell inhibitory function (PubMed:30580966). Following TCR engagement, LAG3 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (PubMed:12209638, PubMed:12421911, PubMed:12672063, PubMed:15100286, PubMed:15634887). May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1, possibly by acting as a coreceptor for PDCD1/PD-1 (PubMed:21300912). Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells (PubMed:12209638, PubMed:12421911, PubMed:12672063, PubMed:15100286, PubMed:15634887). Also mediates immune tolerance: constitutively expressed on a subset of regulatory T-cells (Tregs) and contributes to their suppressive function (PubMed:15485628). Also acts as a negative regulator of plasmacytoid dendritic cell (pDCs) activation (PubMed:19201841). Binds MHC class II (MHC-II); the precise role of MHC-II-binding is however unclear (PubMed:12209638, PubMed:12421911, PubMed:15634887). May function as a ligand for MHC class II (MHC-II) on antigen-presenting cells (APC), promoting APC activation/maturation and driving Th1 immune response. Interacts with MHC class II (MHC-II); selectively recognizes stable complexes of peptide and MHC-II (PubMed:12209638, PubMed:12421911, PubMed:30349037). Interacts with FGL1 (via the Fibrinogen C-terminal domain) (PubMed:30580966). Produced following cleavage of the main chain. Primarily expressed in activated CD4(+) and CD8(+) T-cells (PubMed:12209638). Also expressed in a subset of regulatory T-cells (Tregs), such as natural CD4(+)CD25(+) Tregs (PubMed:15485628). Also expressed on plasmacytoid dendritic cells (pDCs) (PubMed:19201841). The KIEELE motif is required for interaction with downstream signaling molecules. Proteolytically cleaved by ADAM10 and ADAM17 within the connecting peptide region, leading to release of Secreted lymphocyte activation gene 3 protein (sLAG-3) (PubMed:17245433). ADAM10 mediates constitutive cleavage, but cleavage increases following T-cell activation, whereas shedding by ADAM17 is induced by TCR signaling in a PRKCQ-dependent manner (PubMed:17245433). Mice develop normally but show minor defects in the natural killer (NK) cells (PubMed:8602528). They are however prone to development of autoimmune diseases, such as autoimmune diabetes on a permissive genetic background (PubMed:21300912, PubMed:21873518). Knockout NOD mice exhibit accelerated, invasive insulitis, corresponding to increased CD4(+) and CD8(+) T-cell islet infiltration and intraislet proliferation (PubMed:21873518). T-cells display a delay in cell cycle arrest following stimulation with the superantigen staphylococcal enterotoxin-B resulting in increased T-cell expansion and splenomegaly (PubMed:15100286). Mice lacking both Lag3 and Pdcd1/PD-1 die of severe myocarditis before 10 weeks of age in BALB/c mice (PubMed:21300912). Belongs to the LAG3 family. An initial knockout experiment in mouse reported only minor phenotype with no development of spontaneous disease, arguing against a significant role in controlling T-cell activation (PubMed:8602528). However, subsequent analysis showed that knockout mice develop autoimmune diseases caused by T-cell activation (PubMed:21873518).