CH2 and CH3 domain deleted IgG1 paraproteins inhibit differently Fc receptor mediated binding and cytolysis

Domain deleted paraproteins are suitable tools to study the interaction between IgG domains and Fc receptor (FcR) binding sites. The effect of the C gamma 2 or C gamma 3 domain deleted paraproteins was compared on antibody dependent cellular cytotoxicity (ADCC) and on FcR mediated rosette formation. The C gamma 2 domain deleted paraprotein (TIM) had no significant effect on lymphocyte or monocyte mediated ADCC, while the C gamma 3 domain deleted paraprotein (SIZ) inhibited both types of cytotoxicity. FcR dependent rosette formation was also inhibited by SIZ but TIM was ineffective. The data further confirm our previous results suggesting a significant role of C gamma 2 domain in the transfer of killing signal in ADCC and that of C gamma 3 domain in the high affinity binding to lymphocyte FcR.