Interaction of Plasmodium falciparum histidine-rich protein II with human lymphocytes leads to suppression of proliferation, IFN-gamma release, and CD69 expression.
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 (125)I to study the specific binding with T and B cells. We found that the binding of (125)I-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 5.61x10(-11)M, and the low affinity class had a K(d) of 8.58x10(-11) M. For the B cells, the high and low affinity classes had a K(d) of 1.32x10(-11) and 2.84x10(-11) M, respectively. Dot-blot, autoradiography, and Western blot analysis also confirmed the specific binding of HRP II with lymphocytes. HRP II significantly inhibited (approximately 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-gamma 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.
Das
Padmalaya
P
Malaria Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, P.O. Box No. 10504, New Delhi, 110067, India. padmalayad@yahoo.co.in
Grewal
Jasvir S
JS
Chauhan
Virander S
VS
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D000953:Antigens, Protozoan / Q000235:genetics* / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007700:Kinetics; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology*; D010963:Plasmodium falciparum; D015800:Protozoan Proteins / Q000235:genetics* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000953:Antigens, Protozoan; D007371:Interferon-gamma; D037181:Lectins, C-Type; D015800:Protozoan Proteins; D000099192:CD69 Antigens; C514457:HRP-2 antigen, Plasmodium falciparum