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. Author manuscript; available in PMC: 2022 Jul 5.
Published in final edited form as: Nat Immunol. 2018 Dec 1;19(12):1278–1279. doi: 10.1038/s41590-018-0257-1

Figure. LAG-3 binding does not always correlate with MHC II expression.

Figure

(a, left panel) LAG-3 fails to bind MHC II expressed by most plasmacytoid DCs but also mature bone-marrow-derived B cells, despite high levels of MHC II expression by these cells. Maruhashi et al. show that this is because LAG-3 does not bind to unstable MHC II/peptide complexes (left panel). (Right panel) IFNγ triggers expression of the transactivator CIITA, which in turn induces DM expression and peptide editing, the formation of stable MHC II/peptide complexes, and LAG-3 binding, whereupon LAG-3 exerts its inhibitory effects. (b) Ribbon diagrams of HLA-DR (PDB: 1DLH) with the CD4 binding-site12 colored blue and the region influenced by MHC II/peptide complex stability (residues with RMSD >2Å versus the DM-bound DR1 complex9) colored yellow. The structure is shown from the point of view of the T-cell receptor (top panel) and from the side (i.e. rotated 90°; bottom panel).