Immune checkpoint REULR. (A) Schematic
representation of PD1-REULR-mediated
PD-1 degradation. (B–D) HEK293T cells were transiently transfected
with FLAG-tagged full-length PD-1 cDNA (human) under the control of
a constitutively active CMV (cytomegalovirus) promoter. 24 h post-transfection,
cells were incubated with PD1-REULR molecules (50 nM), as indicated
using RNF128 (E1; E2)-, RNF130 (A1; D1)-, or RNF167 (A5)-targeting
nanobodies fused to a PD-1 binding nanobody (PD1). Monomeric binding
moieties or PBS were used as negative controls. After 24 h, cells
were subjected to FACS analysis using a FLAG antibody (Alexa Fluor
647 conjugate) to monitor PD-1 levels on the cell surface. Representative
FACS histograms are visualized below the quantified data. Data are
mean ± s.d. (n = three replicates).