The monocyte binding domain(s) on human immunoglobulin G

Monocyte binding has previously been assigned to the C_γ3 domain of human immunoglobulin G (IgG) largely on the ability of the pFc' fragment to inhibit the monocyte-IgG interaction. This ability is markedly reduced compared to the intact parent IgG. We find this result with a conventional pFc' preparation but this preparation is found to contain trace contamination of parent IgG as demonstrated by reactivity with monoclonal antibodies directed against Cγ2 domain and light-chain epitopes of human IgG. Extensive immunoaffinity purification of the pFc' preparation removes its inhibitory ability indicating that this originates in the trace contamination of parent IgG (or Fc). Neither of the human IgG1 paraproteins TIM, lacking the Cγ2 domain, or SIZ, lacking the Cγ3 domain, are found to inhibit the monocyte-IgG interaction. The hinge-deleted IgGI Dob protein shows little or no inhibitory ability. Indirect evidence for the involvement of the Cy2 domain in monocyte binding is considered. We suggest finally that the site of interaction is found either on the Cγ2 domain alone or between the Cγ2 and Cγ3 domains.