Inhibition of the presentation of dengue virus antigen by macrophages to B cells by serine-protease inhibitors

Abstract

It has been shown that macrophages (Mφ) process dengue type 2 virus (DV) antigen and present it to B cells leading to their clonal expansion as shown by DV-specific IgM antibody plaque-forming cell (PFC) count in spleen. The present study was undertaken to find out the nature of enzymes responsible for the processing of DV antigen in Mφ. DV-pulsed Mφ were treated with seven different protease inhibitors and then assayed for antigen presentation to B cells. It was observed that maximum inhibition occurred by treatment of Mφ with PMSF, a serine-protease inhibitor. The effect of PMSF was dose dependent and was abolished by using predigested antigen. PMSF inhibited presentation of DV and sheep RBC antigens but had no effect on presentation of bovine serum albumin which does not require processing. The results thus identify the serine group of proteases as the main enzymes involved in processing the DV antigen in Mφ.