Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Structure of LAG3 reveals key binding sites for immunomodulatory ligands

Crystal structures of the immune checkpoint protein LAG3 reveal critical binding interfaces for inhibitory antibodies and cellular ligands, such as FGL1 and MHC class II molecules. These structures provide insight into the dimeric assembly of LAG3 proteins on the surface of T cells and suggest FGL1-induced clustering as an immunomodulatory mechanism.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: LAG3 structure and FGL1-induced clustering mechanism.

References

  1. Huard, B. et al. Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proc. Natl Acad. Sci. USA 94, 5744–5749 (1997). A mutational mapping study that defines the binding site of MHC class II molecules on the LAG3 protein.

    CAS  Article  Google Scholar 

  2. Wang, J. et al. Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3. Cell 176, 334–347 (2019). This Article reports the discovery and characterization of FGL1 as a LAG3 ligand.

    CAS  Article  Google Scholar 

  3. Tawbi, H. A. et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N. Eng. J. Med. 386, 24–34 (2022). An Article describing the efficacy of a combination therapy with LAG3 and PD-1 inhibitors for advanced melanoma.

    CAS  Article  Google Scholar 

  4. Angin, M. et al. A LAG-3-specific gonist ntibody for the treatment of T cell–induced autoimmune diseases. J. Immunol. 208, 810–818 (2020). This Article characterizes a LAG3 agonist antibody in a model of autoimmune disease.

    Article  Google Scholar 

  5. Maruhashi, T. et al. LAG-3: from molecular functions to clinical applications. J. Immunother. Cancer 8, e001014 (2020). A Review discussing the immunosuppressive mechanisms of LAG3 and its potential as a therapeutic target.

    Article  Google Scholar 

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: Luca, V. C. et al. LAG3 ectodomain structure reveals functional interfaces for ligand and antibody recognition. Nat. Immunol. https://doi.org/XXX (2022).

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Structure of LAG3 reveals key binding sites for immunomodulatory ligands. Nat Immunol 23, 1004–1005 (2022). https://doi.org/10.1038/s41590-022-01242-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41590-022-01242-x

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing