| First Author | Adam K | Year | 2024 |
| Journal | J Immunol | Volume | 213 |
| Issue | 1 | Pages | 7-13 |
| PubMed ID | 38775415 | Mgi Jnum | J:350305 |
| Mgi Id | MGI:7662792 | Doi | 10.4049/jimmunol.2300673 |
| Citation | Adam K, et al. (2024) Cutting Edge: LAG3 Dimerization Is Required for TCR/CD3 Interaction and Inhibition of Antitumor Immunity. J Immunol 213(1):7-13 |
| abstractText | 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. |
