CD4/major histocompatibility complex class II interaction analyzed with CD4- and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins

Eur J Immunol. 1995 Sep;25(9):2718-21. doi: 10.1002/eji.1830250949.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD*
  • Base Sequence
  • Binding, Competitive
  • CD4 Antigens / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytotoxicity, Immunologic / drug effects
  • Histocompatibility Antigens Class II / immunology*
  • Membrane Proteins / immunology*
  • Membrane Proteins / pharmacology
  • Mice
  • Molecular Sequence Data
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / pharmacology

Substances

  • Antigens, CD
  • CD223 antigen
  • CD4 Antigens
  • Histocompatibility Antigens Class II
  • Membrane Proteins
  • Recombinant Fusion Proteins