{Reference Type}: Journal Article
{Title}: Cutting Edge: LAG3 Dimerization Is Required for TCR/CD3 Interaction and Inhibition of Antitumor Immunity.
{Author}: Adam K;Lipatova Z;Abdul Ghafoor Raja M;Mishra AK;Mariuzza RA;Workman CJ;Vignali DAA;
{Journal}: J Immunol
{Volume}: 213
{Issue}: 1
{Year}: 2024 07 1
{Factor}: 5.426
{DOI}: 10.4049/jimmunol.2300673
{Abstract}: Lymphocyte activation gene 3 (LAG3) is an inhibitory receptor that plays a critical role in controlling T cell tolerance and autoimmunity and is a major immunotherapeutic target. LAG3 is expressed on the cell surface as a homodimer but the functional relevance of this is unknown. In this study, we show that the association between the TCR/CD3 complex and a murine LAG3 mutant that cannot dimerize is perturbed in CD8+ T cells. We also show that LAG3 dimerization is required for optimal inhibitory function in a B16-gp100 tumor model. Finally, we demonstrate that a therapeutic LAG3 Ab, C9B7W, which does not block LAG3 interaction with its cognate ligand MHC class II, disrupts LAG3 dimerization and its association with the TCR/CD3 complex. These studies highlight the functional importance of LAG3 dimerization and offer additional approaches to therapeutically target LAG3.