Cellular expression and tissue distribution of the human LAG-3-encoded protein, an MHC class II ligand

  title={Cellular expression and tissue distribution of the human LAG-3-encoded protein, an MHC class II ligand},
  author={Bertrand Huard and Philippe Gaulard and Florence Faure and Thierry Hercend and Frederic Triebel},
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 (Triebel et al. 1990). The characterization of genomic clones encompassing the LAG-3 locus revealed that the position of the introns in the LAG-3 structure is very close to that of CD4 and that both genes include an intron within the first immunoglobulin superfamily (IgSF) domain. In addition, both genes are located on the distal part… Expand
Biochemical Analysis of the Regulatory T Cell Protein Lymphocyte Activation Gene-3 (LAG-3; CD223)1
This study shows that LAG-3 is cleaved within the D4 transmembrane domain connecting peptide into two fragments that remain membrane associated, which may contribute to the function of this key regulatory T cell protein. Expand
Lymphocyte activation gene-3 : the expression and function in the immune system
The main finding of this work is that, unlike previously thought, LAG-3 expression is not only limited to activated T and NK cells, but can also be induced on B cells and DCs, which suggests a novel co-stimulatory function of L AG-3 on APCs. Expand
Trafficking of LAG-3 to the Surface on Activated T Cells via Its Cytoplasmic Domain and Protein Kinase C Signaling
Results indicated that the cytoplasmic domain without Glu-Pro repetitive sequence is critical for the translocation of LAG-3 from lysosomal compartments to the cell surface through protein kinase C signaling in activated T cells. Expand
Differential subcellular localization of the regulatory T‐cell protein LAG‐3 and the coreceptor CD4
The substantial intracellular storage of LAG‐3 and its close association with the microtubule organizing center and recycling endosomes may facilitate its rapid translocation to the cell surface during T‐cell activation and help to mitigate T‐ cell activation. Expand
Phenotypic analysis of the murine CD4‐related glycoprotein, CD223 (LAG‐3)
It is shown that mRNA expression is restricted to the thymic medulla, splenic red pulp and sparse cells in the adult brain cortex, and a new monoclonal antibody (mAb) that recognizes an epitope in the D2 domain should greatly assist in the elucidation of CD223 function. Expand
Cutting Edge: Molecular Analysis of the Negative Regulatory Function of Lymphocyte Activation Gene-31
It is shown that LAG-3 inhibitsCD4-dependent, but not CD4-independent, T cell function via its cytoplasmic domain, and a single lysine residue within a conserved “KIEELE” motif is essential for interaction with downstream signaling molecules. Expand
Maturation and Activation of Dendritic Cells Induced by Lymphocyte Activation Gene-3 (CD223)1
The effect of LAG-3Ig on the maturation and activation of human monocyte-derived dendritic cells (DC) is reported, which increases the capacity of DC to stimulate the proliferation and IFN-γ response by allogeneic T cells. Expand
MHC class II signal transduction in human dendritic cells induced by a natural ligand, the LAG-3 protein (CD223).
The signal transduction pathways involved in the LAG-3-induced maturation of human monocyte-derived DCs are investigated and studies using inhibitors demonstrate that these 3 pathways are all important in inducing the maturation process of LAG -3-stimulated DCs. Expand
LAG-3 Regulates Plasmacytoid Dendritic Cell Homeostasis1
The data suggests that LAG-3 plays an important but selective cell intrinsic and cell extrinsic role in pDC biology, and may serve as a key functional marker for their study of homeostatic reciprocity between T cells and pDCs. Expand
Negative Regulation of T Cell Homeostasis by Lymphocyte Activation Gene-3 (CD223)1
It is shown that aged mice deficient in lymphocyte activation gene 3 (LAG-3), an MHC class II binding CD4 homologue, have twice as many T cells as wild-type controls and deregulation of T cell homeostasis by regulatory T cell-dependent and independent mechanisms is suggested. Expand


LAG-3, a novel lymphocyte activation gene closely related to CD4
The compared analysis of LAG-3 and CD4, with respect to both their peptidic sequence as well as their exon/intron organization, indicated that the two molecules are closely related. Expand
Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens
It is demonstrated that rosette formation between LAG-3-transfected COS-7 cells and human leukocyte antigen (HLA) class II-bearing B lymphocytes is specifically dependent on L AG-3/HLA class II interaction. Expand
An 'alternative' pathway of T cell activation.
Based on their functions one can begin to understand the biological significance of a critical accessory receptor-induced pathway (initially proposed as an 'alternative' pathway of T cell activation) which contributes to human T lymphocyte growth and differentiation. Expand
Combination of interleukin-2 and gamma interferon in metastatic renal cell carcinoma.
Immunological profile observed with this regimen showed a major increase in natural killer cells which became the predominant lymphocyte population at the end of the therapy, increasing acceptability of the regimen by the patients. Expand