Linkage group selection: Towards identifying genes controlling strain specific protective immunity in malaria

Abstract

Protective immunity against blood infections of malaria is partly specific to the genotype or stain of the parasites. The target antigen 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 compsite Plasmodium chabaudi chabaudi. In a previod suth analysis using the progeny of a genetic cross between P. c, chabaudi lines AS-pyr1 and CB, a location an P. c. chabaudi chromosome 8 containing the gene for merozoite surface protein-1, a known candidate antigen for Strain Specific Proteitive immunity, was strongly selected. P, c, chabaudi apical membrane antigen-1, another cindidate for Strain Specific Protective Immunity, could not have been evaluated in this cross as AS-pyrl 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-pyrl10 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-t 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. © 2007 Pattaradilokrat et al.