Fig. 3: LAG3 and CD4 bind to overlapping interfaces on MHC-II.
From: Structural basis for mouse LAG3 interactions with the MHC class II molecule I-Ab
a Alignment of scLAG3-MHC-II and CD4-MHC-II (PDB 1JL4)30 structures indicates that LAG3 (cyan) and CD4 (yellow) share a binding site on MHC-II. The MHC-II α and β chains are shown in light and dark grey, respectively. The approach angle of CD4 D1-D2 is tilted by ∼25° compared to LAG3 D1-D2. b The regions surfaces bound by LAG3 (left, cyan) and CD4 (right, yellow) are painted onto the surface of MHC-II molecules. The LAG3-MHC-II interface buries nearly double the amount of surface area (1012 Å2) of that buried by the CD4-MHC-II interface (512 Å2). c Raji APC cells were stained with fluorescently labeled LAG3 tetramers (20 nM) in the presence or absence of 1 µM CD4HA competitor. The control represents Raji APC cells incubated with streptavidin 647 only. Data are shown as normalized median MFI ± SEM based on triplicate wells from two independent experiments (n = 2). Open and closed circles represent data points from each independent experiment. Statistics were obtained using a one-way ANOVA multiple comparison in Prism 9 (Version 9.5.1). d BLI sensograms depict the binding of immobilized CD4HA to HLA-DR4 molecules loaded with an HIV peptide (DR4HIV)42 in the presence of hLAG3-Fc protein (5 μM) or Fc control protein (5 μM). The plot depicts a representative sensogram from two independent experiments. Source data are provided as a Source Data file.
