Figure 4.
In vitro characterization of WT and R47H TREM2. A, reduced binding of R47H TREM2 ECD compared with WT ECD as measured by ELISA. TREM1 ECD is used as a nonbinding control. B, PS-mediated activation of pSyk in HEK cells expressing R47H TREM2 is reduced compared with cells expressing WT TREM2. C, dynamic light scattering diagram of hydrodynamic radius (nm) versus intensity (%) of WT TREM2 and WT TREM2 incubated with PS and of R47H TREM2 variant incubated with PS revealed a hydrodynamic radius of 20 Å (black) for WT and 16 Å (blue) for the variant. The addition of PS shifts WT TREM2 ECD to a high-order oligomer with a radius of 35 Å (green); no shift is observed for the R47H variant (black dots). PS-only control is depicted in pink.