Cutting edge: Molecular analysis of the negative regulatory function of lymphocyte activation gene-3

Academic Article


  • Lymphocyte activation gene (LAG)-3 (CD223) is a CD4-related activation-induced cell surface molecule that binds to MHC class II molecules with high affinity and negatively regulates T cell expansion and homeostasis. In this study, we show that LAG-3 inhibits CD4-dependent, but not CD4-independent, T cell function via its cytoplasmic domain. Although high affinity interaction with MHC class II molecules is essential for LAG-3 function, tailless LAG-3 does not compete with CD4 for ligand binding. A single lysine residue (K468) within a conserved "KIEELE" motif is essential for interaction with downstream signaling molecules. These data provide insight into the mechanism of action of this important T cell regulatory molecule.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Workman CJ; Dugger KJ; Vignali DAA
  • Start Page

  • 5392
  • End Page

  • 5395
  • Volume

  • 169
  • Issue

  • 10