Rat and human natural killers exhibit contrasting immunoglobulin G subclass specificities in antibody-dependent cellular cytotoxicity reflecting differences in their Fc receptors (Fc gamma R).

Rat and human natural killers (rtNK and huNK, respectively) were compared in quantitative antibody-dependent cellular cytotoxicity (ADCC) assays for their capacity to recognize mouse and rat IgG monoclonal antibodies (MAb) of different subclasses. NK from these two species exhibit considerably different patterns of IgG subclass recognition as determined by the relative antibody concentrations required for comparable levels of target cells lysis. ADCC assays with a panel of 16 MAb revealed that the efficiency of rtNK-mediated target lysis diminished according to IgG subclass in the following order: molgG1 greater than rtlgG2a greater than molgG2b approximately molgG2a greater than rtlgG2b greater than molgG3. By comparison, huNK recognized the same antibodies with nearly the opposite order of efficiency: rtlgG2b much greater than molgG2a greater than molgG3 greater than molgG2b much greater than rtlgG2a approximately molgG1. Only molgG2a antibodies were equally potent with rtNK and huNK. The contrasting difference in IgG subclass recognition by rat and human NK reflects the comparatively low protein sequence homology between their respective IgG Fc receptors (Fc gamma R).