Polytuftsin: its possible effects and mechanism during macrophage activation

Polytuftsin (PT) a 35-40 repeat unit of tuftsin (TKPR), when administered as a conjugate with the malarial peptide, ring-infected erythrocyte surface antigen (RESA), enhanced antigen-induced lymphoproliferation and antibody levels in mice as compared to RESA alone. This enhancement was unrelated to the H-2 background of the animals. The present study was undertaken with a view to understanding the mechanism(s) responsible for this immune enhancement. Peritoneal adherent cells (PAC) from H-2b and H-2d mice were incubated with RESA alone, PT-conjugated RESA, a physical mixture of RESA + PT and PT alone. They were subsequently evaluated for I-A expression using monoclonal antibodies and flow cytometry as well as cell-ELISA. Significant increase in I-A expression on PAC was observed in all 4 groups as compared to untreated cells. Whereas cells treated with PT-conjugated RESA showed highly significant increase in I-A (P < 0.001), the other groups showed moderate increase (P < 0.05). This enhancement was attributable to increase in the number of I-A-positive cells rather than I-A molecules per cell. Moreover, IL-1 release, as assayed by bioassay, was significantly higher in cells treated with conjugated RESA as compared to cells treated with RESA or PT alone (P < 0.05). Thus, it would appear that PT-conjugated RESA peptide of the malarial antigen selectively enhances major histocompatibility complex (MHC) class II molecules on antigen-presenting cells (APC) and may therefore improve immune functions by stimulating better antigen presentation and proliferation of T cells.