Interaction of Plasmodium falciparum histidine-rich protein II with human lymphocytes leads to suppression of proliferation, IFN-γ release, and CD69 expression

Abstract

The presence of histidine-rich protein II (HRP II) synthesized by Plasmodium falciparum in the plasma of malaria patients for longer periods even after parasite clearance raises questions about its extracellular functions. The present study was carried out to examine its influence on host immune system. Recombinant HRP-II protein was radiolabeled with ¹²⁵I to study the specific binding with T and B cells. We found that the binding of ¹²⁵I-HRP II with human T and B cells was specific, concentration dependent, saturable, and reversible. Scatchard plot analysis revealed two classes of binding sites for both T and B cells. For the T cells, the high affinity class had dissociation constant (K_d) of 5.61 × 10^-11 M, and the low affinity class had a K_d of 8.58 × 10^-11 M. For the B cells, the high and low affinity classes had a K_d of 1.32 × 10^-11 and 2.84 × 10^-11 M, respectively. Dot-blot, autoradiography, and Western blot analysis also confirmed the specific binding of HRP II with lymphocytes. HRP II significantly inhibited (~75%) T-cell rosette formation with sheep erythrocytes. HRP II also suppressed proliferation of T and B cells triggered by CD3 and LPS, respectively. We found a reduction in IFN-γ release in T cells preincubated with HRP II. HRP II also reduced the CD69 expression on the T cells. In conclusion, HRP-II binding to human lymphocytes leads to suppression of some of their functions