Lymphocyte activation gene 3 protein
LAG-3
Alternative names | CD223 |
Known ligands | MHC II |
Origin | Homo sapiens |
Accession number | P18627 |
LAG-3 is a 498-amino acid, type I transmembrane protein. It consists of four immunoglobulin superfamily-like domains, exhibiting highly similar folding pattern to CD4. It occurs on activated T-cells’ surface as dimeric, whereas soluble form is monomeric (1). LAG-3 binds to MHC II through 30 amino acid loop (2). Soluble form does not appear to bind to MHC II. LAG-3 signaling mechanism is still unknown. Unique for LAG-3 is KIEELE motif, which is highly conserved between species and therefore it is hypothetized that it is essential for the protein’s activity (3). LAG-3 is a negative regulator of T-cell activation. It promotes Treg differentiation, while its blockade inhibits Treg induction (4).
- Andrews, L. P., Marciscano, A. E., Drake, C. G., & Vignali, D. A. (2017). LAG 3 (CD 223) as a cancer immunotherapy target. Immunological reviews, 276(1), 80-96.
- Huard, B., Mastrangeli, R., Prigent, P., Bruniquel, D., Donini, S., El-Tayar, N., … & Triebel, F. (1997). Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proceedings of the National Academy of Sciences, 94(11), 5744-5749.
- Workman, C. J., Dugger, K. J., & Vignali, D. A. (2002). Cutting edge: molecular analysis of the negative regulatory function of lymphocyte activation gene-3. The Journal of Immunology, 169(10), 5392-5395.
- Durham, N. M., Nirschl, C. J., Jackson, C. M., Elias, J., Kochel, C. M., Anders, R. A., & Drake, C. G. (2014). Lymphocyte Activation Gene 3 (LAG-3) modulates the ability of CD4 T-cells to be suppressed in vivo. PloS one, 9(11), e109080.