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 t he 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 imm unization experiments. Initial comparison of two PIM cDNA. sequences s uggested that the PIM genes consist of conserved 5' and 3' termini fla nking a central variable region. We present further evidence, based on sequence analysis, supporting this general structure for the PIM gene s. Evidence is also presented for a single copy of the PIM gene per ha ploid genome, implying that the different versions of PIM are encoded by distinct alleles. The central variable region of the PIM allele fro m the T. parva (Marikebuni) stock was found to contain 13 copies of th e tetrapeptide repeat Gln-Pro-Glu-Pro. We also detected point mutation s in the 5' and 3' termini of the PIM alleles, including regions recog nized by the neutralizing and typing mAb. This contrasted with the hig h sequence conservation of the two introns of the genes, suggesting th at the protein is undergoing rapid evolution. Sequence comparison of P IM genes from buffalo- and cattle-derived parasites supported earlier results that the parasites infecting buffaloes constitute a more heter ogeneous population than those from cattle.