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

Int Immunol. 1999 Nov;11(11):1745-52. doi: 10.1093/intimm/11.11.1745.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antigens, CD*
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism*
  • Fluorescent Antibody Technique
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Ligands
  • Lymphocyte Activation Gene 3 Protein
  • Lymphocyte Activation*
  • Membrane Proteins / metabolism*
  • Mice
  • Peptides / immunology
  • Peptides / metabolism
  • Receptor-CD3 Complex, Antigen, T-Cell / immunology
  • Receptor-CD3 Complex, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • CD8 Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Ligands
  • Membrane Proteins
  • Peptides
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Lymphocyte Activation Gene 3 Protein