Structure and sequence variation of the genes encoding the polymorphic, immunodominant molecule (PIM), an antigen of Theileria parva recognized by inhibitory monoclonal antibodies

The polymorphic, immunodominant molecule (PIM) of Theileria parva is the predominant antigen recognized by sera from infected cattle and by monoclonal antibodies (mAb) used to differentiate parasite strains. As such, the antigen is under consideration as a diagnostic antigen, and since the mAbs can neutralize sporozoite infectivity in vitro, in immunization experiments. Initial comparison of two PIM cDNA sequences suggested that the PIM genes consist of conserved 5' and 3' termini flanking a central variable region. We present further evidence, based on sequence analysis, supporting this general structure for the PIM genes. Evidence is also presented for a single copy of the PIM gene per haploid genome, implying that the different versions of PIM are encoded by distinct alleles. The central variable region of the PIM allele from the T. parva (Marikebuni) stock was found to contain 13 copies of the tetrapeptide repeat Gln-Pro-Glu-Pro. We also detected point mutations in the 5' and 3' termini of the PIM alleles, including regions recognized by the neutralizing and typing mAb. This contrasted with the high sequence conservation of the two introns of the genes, suggesting that the protein is undergoing rapid evolution. Sequence comparison of PIM genes from buffalo- and cattle-derived parasites supported earlier results that the parasites infecting buffaloes constitute a more heterogeneous population than those from cattle