Role of the Polymorphic Immunodominant Molecule in Entry of Theileria parva Sporozoites into Bovine Lymphocytes

Abstract

Theileria parva is a tick-transmitted apicomplexan parasite that infects cattle and African buffalo. In cattle, it causes a fatal lymphoproliferative disease called East Coast fever. The polymorphic immunodominant molecule (PIM) is expressed by two stages of the parasite: the sporozoite, which is inoculated by the tick to infect mammalian lymphocytes, and the schizont, the established intralymphocytic stage. Here, we demonstrate that monoclonal antibodies (MAb) to PIM can reduce the ability of sporozoites to infect bovine lymphocytes in vitro. This reduction appears to be due to blocking of sporozoite attachment by binding of the MAb to several regions of PIM. Interestingly, one MAb, which recognizes an epitope in the central variable region of PIM, did not inhibit sporozoite infectivity. We also demonstrate that PIM antigen, as a recombinant molecule, can also reduce sporozoite infectivity in vitro by blocking both attachment and internalization of sporozoites. Electron microscopic studies showed that PIM is present in microspheres below the sporozoite surface and is transported to the parasite surface soon after contact with bovine lymphocytes. The results suggest that at least two sporozoite molecules, PIM and the previously described p67, are involved in the entry of T. parva into mammalian lymphocytes.

Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines

“…-IFN-γ expression in CD4 + T cells [66] Babesia spp. Rhoptry-Associated Protein (RAP-1) Antigen-specific IgG and IFN-γ release [72] Heat-shock protein 20 (Hsp 20) T cell proliferation and IFN-γ production [71] B. microti surface antigen (BMSA) Th17 and Th2 activation and IgG1 secretion [73] B. divergens Apical Membrane Antigen-1 (BdAMA-1) IgG1, IgG2, Th1 and Th2 activation [74] B. bovis rhoptry neck protein 2 (RON2) Induction of partially neutralizing antibodies that blocked the invasion process [79] Chimeric multi-antigen Antigen-specific IgG1, CD4 + and CD8 + IFN-γ + [81][82][83] Theileria parva Tp1-Tp2-Tp4-Tp5-Tp7-Tp8 CD8 + T-cell responses [92,[94][95][96][97][98][99][100][101] p67 Ab production [102] Polymorphyc immunodominant molecule (PIM) Production of Ab with neutralizing activity [103,104] p150 Ab production…”

Approaches to vaccination against Theileria parva and Theileria annulata

“…A 108 amino acid C-terminal peptide of SPAG1 fused to hepatitis B core antigen has also been shown to induce immunity equivalent to that of full-length SPAG1. 89 The polymorphic immunodominant molecule (PIM) in T. parva is also a target of murine nmAbs, 96,97 Herein, we will explore this further to consider whether there is scope for inducing protective responses that are active against both parasite species.…”

“…The polymorphic immunodominant molecule (PIM) in T. parva is also a target of murine nmAbs, but as cattle do not make neutralizing antibodies to full‐length recombinant PIM, this antigen has not been tested in challenge experiments . PIM is expressed in both sporozoites and schizonts.…”

Gene gun DNA immunization of cattle induces humoral and CD4 T-cell-mediated immune responses against the Theileria parva polymorphic immunodominant molecule

“…PIM is comprised of a central variable region flanked by conserved N- and C-terminal ends, ranges in size (based on strain) from 62 kDa, and is a good model of structurally-complex protozoal proteins [29] . PIM is highly expressed by both the sporozoite and schizont stages [30] and plays a role in sporozoite lymphocyte entry during early infection [31] . As its name implies, PIM is the target of vigorous immune responses during T. parva infection [32] .…”