Fig. 5: CTLA-4 Arg70 mutations allow binding to CD80 but not CD86. | Nature Immunology

Fig. 5: CTLA-4 Arg70 mutations allow binding to CD80 but not CD86.

From: Differences in CD80 and CD86 transendocytosis reveal CD86 as a key target for CTLA-4 immune regulation

Fig. 5

a, Patient-identified CTLA-4 mutations resulting in ligand-facing amino acid changes (red) mapped to CTLA-4 (ribbon structure) and the location of bound CD80 (blue space-filling structure). The right-hand structure shows a view after 90° rotation. b, FACS analysis of CD80–Ig binding and CD86–Ig binding to CTLA-4 WT or mutant proteins (Arg70Gln, Arg70Trp, Cys85Tyr, Ala86Val and Pro137Arg) expressed in CHO cells. Binding of Ig fusions to CTLA-4 (x axis) at 37 °C for 1 h is plotted against a co-stain for total CTLA-4 (y axis) using a cytoplasmic (C-term) domain antibody (C-19). Staining of CTLA-4− control cells is shown in the red contours. c, Mutant CTLA-4 Ig proteins (Arg70Gln, Arg70Trp) or CTLA-4 WT Ig was used to stain CD80–GFP- and CD86–GFP-expressing CHO cells. Red contours show anti-Ig control staining in the absence of CTLA-4 Ig. d, Calculated monomeric affinity of the CD80–CTLA-4–Arg70Gln interaction, based on binding of soluble monomeric CD80 to immobilized Arg70Gln–Ig on the sensor. e, Calculated monomeric affinity of the CD86–CTLA-4–Arg70Gln interaction, based on binding of soluble monomeric CD86 to immobilized Arg70Gln–Ig on the sensor.

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