PT - JOURNAL ARTICLE AU - Workman, Creg J. AU - Dugger, Kari J. AU - Vignali, Dario A. A. TI - Cutting Edge: Molecular Analysis of the Negative Regulatory Function of Lymphocyte Activation Gene-3 AID - 10.4049/jimmunol.169.10.5392 DP - 2002 Nov 15 TA - The Journal of Immunology PG - 5392--5395 VI - 169 IP - 10 4099 - http://www.jimmunol.org/content/169/10/5392.short 4100 - http://www.jimmunol.org/content/169/10/5392.full SO - J. Immunol.2002 Nov 15; 169 AB - 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.