title: CD4/major histocompatibility complex class II interaction analyzed with CD4- and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins.
abstract: We analyzed CD4 major histocompatibility complex (MHC) class II interactions with CD4 and lymphocyte activation gene (LAG)-3 recombinant fusion proteins termed CD4Ig and LAG-3Ig. CD4Ig bound MHC class II molecules expressed on the cell surface only when used in the micromolar range. This weak CD4Ig binding was specific, since it was inhibited by anti-CD4 and anti-MHC class II mAb. LAG-3Ig bound MHC class II molecules with intermediate avidity (Kd = 60 nM at 37 degrees C). Using LAG-3Ig as a competitor in a CD4/MHC class II-dependent cellular adhesion assay, we showed that this recombinant molecule was able to block CD4/MHC class II interaction. In contrast, no inhibition was observed in a CD4/MHC class II-dependent T cell cytotoxicity assay. Together, these results suggest that co-engagement of the TcR with CD4 alters the CD4/MHC class II molecular interaction to become insensitive to LAG-3Ig competition.
authors.affiliation: Laboratoire d'Immunologie Cellulaire, INSERM U333, Institut Gustave-Roussy, Villejuif, France.
authors.forename: B
authors.initials: B
authors.lastname: Huard
authors.forename: P
authors.initials: P
authors.lastname: Prigent
authors.forename: M
authors.initials: M
authors.lastname: Tournier
authors.forename: D
authors.initials: D
authors.lastname: Bruniquel
authors.forename: F
authors.initials: F
authors.lastname: Triebel
mesh_terms: D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse