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Protective immunity against blood infections of malaria is partly specific to the genotype, or strain, of the parasites. The target antigens of Strain Specific Protective Immunity are expected, therefore, to be antigenically and genetically distinct in different lines of parasite. Here we describe the use of a genetic approach, Linkage Group Selection, to locate the target(s) of Strain Specific Protective Immunity in the rodent malaria parasite  Plasmodium chabaudi chabaudi . In a previous such analysis using the progeny of a genetic cross between  P. c. chabaudi  lines AS-pyr1 and CB, a location on  P. c. chabaudi  chromosome 8 containing the gene for merozoite surface protein-1, a known candidate antigen for Strain Specific Protective Immunity, was strongly selected.  P. c. chabaudi  apical membrane antigen-1, another candidate for Strain Specific Protective Immunity, could not have been evaluated in this cross as AS-pyr1 and CB are identical within the cell surface domain of this protein. Here we use Linkage Group Selection analysis of Strain Specific Protective Immunity in a cross between  P. c. chabaudi  lines CB-pyr10 and AJ, in which merozoite surface protein-1 and apical membrane antigen-1 are both genetically distinct. In this analysis strain specific immune selection acted strongly on the region of  P. c. chabaudi  chromosome 8 encoding merozoite surface protein-1 and, less strongly, on the  P. c. chabaudi  chromosome 9 region encoding apical membrane antigen-1. The evidence from these two independent studies indicates that Strain Specific Protective Immunity in  P. c. chabaudi  in mice is mainly determined by a narrow region of the  P. c. chabaudi  genome containing the gene for the  P. c. chabaudi  merozoite surface protein-1 protein. Other regions, including that containing the gene for  P. c. chabaudi  apical membrane antigen-1, may be more weakly associated with Strain Specific Protective Immunity in these parasites.

Linkage Group Selection: Towards Identifying Genes Controlling Strain Specific Protective Immunity in Malaria