A SINGLE AMINO-ACID DETERMINES THE SPECIFICITY OF A MONOCLONAL-ANTIBODY WHICH INHIBITS PLASMODIUM-CHABAUDI AS IN-VIVO

The in vivo inhibitory action of NIMP23, a monoclonal antibody raised against the rodent parasite Plasmodium chabaudi chabaudi ASI has previ ously been shown to be strain-specific, capable of delaying significan tly the onset of P. c. chabaudi AS but not a P. c. chabaudi CB challen ge parasitaemia. The epitope to which this mAb binds has been mapped t o the second of two epidermal growth factor-like domains located al th e C-terminus of the merozoite surface protein 1 (MSP-1) of P. c. chaba udi AS. The C-terminus region of the MSP-1 of P. c. chabaudi is a regi on of heterogeneity with AS and CB strain parasites showing only 78% i dentity at the amino acid level. The critical amino acid substitution which accounts for the strain specificity of the NIMP23 monoclonal ant ibody has now been identified. Polymerase chain reaction directed muta genesis experiments demonstrate that a single proline to asparagine su bstitution at position 1722 in the primary amino acid sequence is suff icient to convert NIMP23-negative P. c. chabaudi CB expression constru cts into NIMP23-positive clones whilst the converse substitution of an asparagine for a proline residue converts P. c. chabaudi AS expressio n constructs into NIMP23-negative clones.