PMID- 8647185
OWN - NLM
STAT- MEDLINE
DCOM- 19960725
LR  - 20221207
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 26
IP  - 5
DP  - 1996 May
TI  - T cell major histocompatibility complex class II molecules down-regulate CD4+ T 
      cell clone responses following LAG-3 binding.
PG  - 1180-6
AB  - T cell response to its antigen requires recognition by the T cell receptor 
      together with a co-receptor molecule, either CD4 or CD8. Additional molecules 
      have been identified that are capable of delivering the co-stimulatory signals 
      provided by APC. Following T cell priming, a number of T cell activation antigens 
      are expressed that may play a role in the inactivation phase of the T cell 
      response. The lymphocyte activation gene (LAG)-3 protein and its 
      counter-receptors, the major histocompatibility complex (MHC) class II molecules, 
      are such activation antigens whose interaction may result in the down-regulation 
      of the ongoing immune response. To investigate the role of LAG-3/class II 
      molecule interaction, we produced a soluble form of LAG-3 by fusing the 
      extracellular Ig domains of this membrane protein to the constant region of human 
      IgG1 (LAG-3Ig). Here, we show a direct and specific binding of LAG-3Ig to class 
      II molecules on the cell surface. In addition, we show that LAG-3/class II 
      molecule interaction leads to the down-regulation of CD4+ Ag-specific T cell 
      clone proliferation and cytokine secretion. This inhibitory effect is observed at 
      the level of the effector cells and not the APC and is also found with anti-CD3 
      mAb, PHA + PMA or low-dose IL-2 driven stimulation in the absence of APC. These 
      functional studies indicate that T cell MHC class II molecules down-regulate T 
      cell proliferation following LAG-3 binding and suggest a role for LAG-3 in the 
      control of the CD4+ T cell response.
FAU - Huard, B
AU  - Huard B
AD  - Laboratoire d'Immunologie Cellulaire, INSERM U333, Institut Gustave-Roussy, 
      Villejuif, France.
FAU - Prigent, P
AU  - Prigent P
FAU - Pages, F
AU  - Pages F
FAU - Bruniquel, D
AU  - Bruniquel D
FAU - Triebel, F
AU  - Triebel F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Antigens, CD)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Membrane Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Lymphocyte Activation Gene 3 Protein)
RN  - 0 (Lag3 protein, human)
RN  - 0 (soluble LAG-3 protein, human)
SB  - IM
MH  - *Antigens, CD
MH  - Base Sequence
MH  - CD4-Positive T-Lymphocytes/*immunology/*metabolism
MH  - Clone Cells
MH  - Down-Regulation/*immunology
MH  - Genetic Vectors/immunology
MH  - Histocompatibility Antigens Class II/*physiology
MH  - Humans
MH  - Immunoglobulin G/chemistry/genetics
MH  - Lymphocyte Activation
MH  - Membrane Proteins/*chemistry/immunology
MH  - Molecular Sequence Data
MH  - Protein Binding/immunology
MH  - Recombinant Fusion Proteins/pharmacology
MH  - Lymphocyte Activation Gene 3 Protein
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
AID - 10.1002/eji.1830260533 [doi]
PST - ppublish
SO  - Eur J Immunol. 1996 May;26(5):1180-6. doi: 10.1002/eji.1830260533.