Synthetic Peptides of Human CD4 Enhance Binding of Immunoglobulins to Monocyte/Macrophage Cells: II. Mechanisms of Enhancement

We have previously shown that a synthetic peptide corresponding to amino acid residues 21-49 of the first extracellular domain of human CD4 binds immunoglobulins (Ig) and antibody: antigen (Ab:Ag) complexes, and greatly enhances the uptake of aggregated Ig by monocyte/macrophage U937 cells. In this report, we investigated the mechanisms of enhanced uptake, and the contribution of different receptors present on the surface of monocyte/macrophage cells to this phenomenon. Our results indicate that both Fe receptor (FcR) and cell surface CD4 participate in the enhanced uptake of Ig promoted by the synthetic peptide of CD4. The involvement of these two receptors was demonstrated in experiments using monoclonal antibodies to FcR and CD4, as well as monosialoganglioside GMI, a substance known to modulate surface CD4. The participation of CD4 was further confirmed using the CD4 monocyte/macrophage cell line MM-6. Together, the results of these experiments indicate that surface CD4 may cooperate with FcR in handling aggregated Ig and Ab:Ag complexes. The implications of these findings for immunoregulation by Ab:Ag and idiotype:anti-idiotype (Id:anti-Id) complexes, and infection of macrophages by HIV, are discussed.