PMID- 1380059
OWN - NLM
STAT- MEDLINE
DCOM- 19920916
LR  - 20221207
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 176
IP  - 2
DP  - 1992 Aug 1
TI  - Characterization of the lymphocyte activation gene 3-encoded protein. A new 
      ligand for human leukocyte antigen class II antigens.
PG  - 327-37
AB  - 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. We report here the initial characterization of the LAG-3-encoded protein. 
      We have generated two monoclonal antibodies after immunization of mice with a 
      30-amino acid peptide that corresponds to an exposed extra loop region present in 
      the LAG-3 immunoglobulin-like first domain. 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. 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. Cellular distribution 
      analysis indicated that the LAG-3.1 epitope is expressed on activated T (both 
      CD4+ and CD8+ subsets) and NK cells, and not on activated B cells or monocytes. 
      In immunoprecipitation experiments performed on activated T and NK cell lysates, 
      a 70-kD protein was detected after SDS-PAGE analysis. 45-kD protein species were 
      also immunoprecipitated. Both the 70- and 45-kD proteins were shown to be 
      N-glycosylated. In Western blot analysis, only the former molecule was recognized 
      by the anti-LAG-3 antibodies, demonstrating that it is LAG-3 encoded. These 
      anti-LAG-3 antibodies were used to investigate whether the LAG-3 protein 
      interacts with the CD4 ligands. By using a high-level expression cellular system 
      based on COS-7 cell transfection with recombinant CDM8 vectors and a quantitative 
      cellular adhesion assay, we demonstrate that rosette formation between 
      LAG-3-transfected COS-7 cells and human leukocyte antigen (HLA) class II-bearing 
      B lymphocytes is specifically dependent on LAG-3/HLA class II interaction. In 
      contrast to CD4, LAG-3 does not bind the human immunodeficiency virus gp120. This 
      initial characterization will guide further studies on the functions of this 
      molecule, which may play an important role in immune responses mediated by T and 
      NK lymphocytes.
FAU - Baixeras, E
AU  - Baixeras E
AD  - Laboratoire d'Hemato-Immunologie, INSERM U333, Institut Gustave-Roussy, 
      Villejuif, France.
FAU - Huard, B
AU  - Huard B
FAU - Miossec, C
AU  - Miossec C
FAU - Jitsukawa, S
AU  - Jitsukawa S
FAU - Martin, M
AU  - Martin M
FAU - Hercend, T
AU  - Hercend T
FAU - Auffray, C
AU  - Auffray C
FAU - Triebel, F
AU  - Triebel F
FAU - Piatier-Tonneau, D
AU  - Piatier-Tonneau D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Epitopes)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Ligands)
RN  - 0 (Membrane Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Lymphocyte Activation Gene 3 Protein)
RN  - 0 (Lag3 protein, human)
SB  - IM
GS  - LAG-3
MH  - Amino Acid Sequence
MH  - Antibodies, Monoclonal/immunology
MH  - *Antigens, CD
MH  - B-Lymphocytes/cytology/immunology
MH  - Cell Adhesion
MH  - Cell Line
MH  - Cells, Cultured
MH  - Cloning, Molecular
MH  - Epitopes
MH  - Histocompatibility Antigens Class II/*immunology
MH  - Humans
MH  - Kinetics
MH  - Ligands
MH  - Lymphocyte Activation/*genetics
MH  - Membrane Proteins/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Phenotype
MH  - Precipitin Tests
MH  - Recombinant Proteins/genetics/immunology
MH  - Lymphocyte Activation Gene 3 Protein
PMC - PMC2119326
EDAT- 1992/08/01 00:00
MHDA- 1992/08/01 00:01
PMCR- 1993/02/01
CRDT- 1992/08/01 00:00
PHST- 1992/08/01 00:00 [pubmed]
PHST- 1992/08/01 00:01 [medline]
PHST- 1992/08/01 00:00 [entrez]
PHST- 1993/02/01 00:00 [pmc-release]
AID - 92364535 [pii]
AID - 10.1084/jem.176.2.327 [doi]
PST - ppublish
SO  - J Exp Med. 1992 Aug 1;176(2):327-37. doi: 10.1084/jem.176.2.327.