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. 2022 Jul 26;13:956090. doi: 10.3389/fimmu.2022.956090

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Copyright © 2022 Huo, Wang, Fu, Lu and Liu

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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LAG-3 structure and ligands. LAG-3 consists of extracellular region, transmembrane region and cytoplasmic region. The extracellular domain is composed of four IgSF domains, namely D1, D2, D3 and D4. The D1 domain contains a loop domain rich in proline and an in-chain disulfide bond. In the transmembrane- cytoplasmic part, LAG-3 breaks away from the cell membrane under the action of metalloproteinases ADAM10/17. The cytoplasmic region of LAG-3 consists of three parts: the serine phosphorylation site S454, the highly conserved “KIEELE” motif and the glutamate-proline dipeptide repeat motif (EP sequence). MHC II, Galectin-3, LSECtin and FGL1 are the confirmed ligands of LAG-3 in tumor microenvironment.