Affinity of human IgG subclasses to mouse Fc gamma receptors

Human IgG is the main antibody class used in antibody therapies because of its efficacy and longer half-life, which are completely or partly due to Fc gamma R-mediated functions of the molecules. Preclinical testing in mouse models are frequently performed using human IgG, but no detailed information on binding of human IgG to mouse Fc gamma Rs is available. The orthologous mouse and human Fc gamma Rs share roughly 60-70% identity, suggesting some incompatibility. Here, we report binding affinities of all mouse and human IgG subclasses to mouse Fc gamma R. Human IgGs bound to mouse Fc gamma R with remarkably similar binding strengths as we know from binding to human ortholog receptors, with relative affinities IgG3 > IgG1 > IgG4 > IgG2 and Fc gamma RI >> Fc gamma RIV > Fc gamma RIII > Fc gamma RIIb. This suggests human IgG subclasses to have similar relative FcR-mediated biological activities in mice.