The MHC class II ligand lymphocyte activation gene-3 is co-distributed with CD8 and CD3-TCR molecules after their engagement by mAb or peptide-MHC class I complexes.
Previous studies indicated that signaling through lymphocyte activation gene-3 (LAG-3), a MHC class II ligand, induced by multivalent anti-receptor antibodies led to unresponsiveness to TCR stimulation. Here, lateral distribution of the LAG-3 molecules and its topological relationship (mutual proximity) to the TCR, CD8, CD4, and MHC class I and II molecules were studied in the plasma membrane of activated human T cells in co-capping experiments and conventional fluorescence microscopy. Following TCR engagement by either TCR-specific mAb or MHC-peptide complex recognition in T-B cell conjugates, LAG-3 was found to be specifically associated with the CD3-TCR complex. Similarly, following CD8 engagement LAG-3 and CD8 were co-distributed on the cell surface while only a low percentage of CD4-capped cells displayed LAG-3 co-caps. In addition, LAG-3 was found to be associated with MHC class II (i.e. DR, DP and DQ) and partially with MHC class I molecules. The supramolecular assemblies described here between LAG-3, CD3, CD8 and MHC class II molecules may result from an organization in raft microdomains, a phenomenon known to regulate early events of T cell activation.
Hannier
S
S
Laboratoire d'Immunologie Cellulaire, Institut Gustave-Roussy, and Laboratoire d'Immunologie des tumeurs, Faculté de Pharmacie, Université Paris XI, 92296 Chatenay-Malabry, France.
Triebel
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D008565:Membrane Proteins; D010455:Peptides; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D000093322:Lymphocyte Activation Gene 3 Protein