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.