John L Silberstein, Jasper Du, Kun-Wei Chan, Jessica A Frank, Irimpan I Mathews, Yong Bin Kim, Jia You, Qiao Lu, Jia Liu, Elliot A Philips, Phillip Liu, Eric Rao, Daniel Fernandez, Grayson E Rodriguez, Xiang-Peng Kong, Jun Wang, Jennifer R Cochran
Lymphocyte activation gene-3 (LAG-3) is an inhibitory receptor expressed on activated T cells and an emerging immunotherapy target. Domain 1 (D1) of LAG-3, which has been purported to directly interact with major histocompatibility complex class II (MHCII) and fibrinogen-like protein 1 (FGL1), has been the major focus for the development of therapeutic antibodies that inhibit LAG-3 receptor-ligand interactions and restore T cell function. Here, we present a high-resolution structure of glycosylated mouse LAG-3 ectodomain, identifying that cis-homodimerization, mediated through a network of hydrophobic residues within domain 2 (D2), is critically required for LAG-3 function...
March 19, 2024: Proceedings of the National Academy of Sciences of the United States of America