Immunoglobulin G (IgG) antibodies are important for protection against pathogens and exert effector functions through binding to IgG-Fc receptors (FcγRs) on myeloid and natural killer cells, resulting in destruction of opsonized target cells. Despite interspecies differences, IgG subclasses and FcγRs show substantial similarities and functional conservation between mammals. Accordingly, binding of human IgG (hIgG) to mouse FcγRs (mFcγRs) has been utilized to study effector functions of hIgG in mice. In other applications, such as immunostaining with mouse IgG monoclonal antibodies (mAbs), these cross-reactivities are undesired and prone to misinterpretation. Despite this drawback, the binding of mouse IgG (mIgG) subclasses to human FcγR (hFcγR) classes has never been fully documented. Here, we report detailed and quantifiable characterization of binding affinities for all mIgG subclasses to hFcγRs, including functional polymorphic variants. mIgG subclasses show the strongest binding to hFcγRIa, with relative affinities mIgG2a = mIgG2c > mIgG3 >> mIgG2b, and no binding by mIgG1. hFcγRIIa/b showed general low reactivities to all mIgG (mIgG1> mIgG2a/c > mIgG2b), with no reactivity to mIgG3. A particularly high affinity was observed for mIgG1 to the hFcγRIIa-R131 polymorphic variant. hFcγRIIIa showed lower binding (mIgG2a/c > mIgG3), slightly favouring binding to the hFcγRIIIa-V158 over the F158 polymorphic variant. No binding was observed of mIgG to hFcγRIIIb. Deglycosylation of mIgG1 did not abrogate binding to hFcγRIIa-R131, nor did deglycosylation of mIgG2a/c and mIgG3 prevent hFcγRIa binding. Importantly, deglycosylation of the least cross-reactive mIgG subclass, mIgG2b, abrogated reactivity to all hFcγRs. Together, these data document for the first time the full spectrum of cross-reactivities of mouse IgG to human FcγRs.

免疫球蛋白G（IgG）抗体对于保护病原体和通过与髓样和自然杀伤细胞上的IgG-Fc受体（FcγR）结合发挥作用，发挥重要作用，导致调理过的靶细胞遭到破坏。尽管种间存在差异，但IgG亚类和FcγR在哺乳动物之间显示出实质性的相似性和功能保守性。因此，人IgG（hIgG）与小鼠FcγR（mFcγR）的结合已被用于研究hIgG在小鼠中的效应子功能。在其他应用中，例如用小鼠IgG单克隆抗体（mAbs）进行免疫染色，这些交叉反应是不希望的，并且容易造成误解。尽管存在此缺点，但尚未完全记录小鼠IgG（mIgG）亚类与人FcγR（hFcγR）类的结合。这里，我们报告了所有mIgG亚类与hFcγRs，包括功能性多态性变体的结合亲和力的详细和可量化的表征。mIgG亚类显示出与hFcγRIa的最强结合，相对亲和力为mIgG2a = mIgG2c> mIgG3 >> mIgG2b，并且没有被mIgG1结合。hFcγRIIa/ b对所有mIgG的反应性普遍较低（mIgG1> mIgG2a / c> mIgG2b），而对mIgG3无反应性。观察到mIgG1对hFcγRIIa-R131多态性变体的亲和力特别高。hFcγRIIIa显示较低的结合（mIgG2a / c> mIgG3），与F158多态性变体相比，略微倾向于与hFcγRIIIa-V158结合。没有观察到mIgG与hFcγRIIIb的结合。mIgG1的去糖基化不能消除与hFcγRIIa-R131的结合，mIgG2a / c和mIgG3的去糖基化也不能阻止hFcγRIa的结合。重要的，交叉反应最少的mIgG亚类mIgG2b的去糖基化消除了对所有hFcγR的反应性。这些数据一起首次记录了小鼠IgG与人FcγRs的全交叉反应谱。