Figure 4.

Destabilization of the Fc CH2 domain is associated with increased aggregation propensity at low pH. A CH2 mutant panel was paired with LALA and LALE lower hinge mutations. Fc Tm was determined as the lowest melting event observed by DSF, which for WT human IgG1 CH2 is ~67.5 °C. A relationship between reduced CH2 stability and increased susceptibility for forming aggregates at pH 3.5 was observed.