A Leishmania major response locus identified by interval-specific congenic mapping of a T helper type 2 cell bias-controlling quantitative trait locus

The propensity of naive CD4 T cells to become T helper (Th) type 2 cells correlates with susceptibility to infection by the protozoal parasite Leishmania major. Using genetic linkage analysis, we earlier identified Dice 1 as a Th2 cell bias-controlling quantitative trait locus on chromosome 16. Using interval-specific congenic mapping, we now resolve Dice 1 into two independent genetic loci, Dice 1.1 and Dice 1.2, which control Il4 expression front naive Th cells and thereby indirectly control Th2 cell bias. Interestingly, only one of the two congenic intervals containing Dice 1.1 and Dice 1.2, respectively, also contained an L. major response locus, indicating that L. Major responsiveness can be insensitive to determinants that influence Th2 cell bias by controlling naive T cell Il4 expression. These results lay the groundwork for identifying the Dice 1.1 and Dice 1.2 genes controlling naive T cell Il4 expression and L. major responses, and for testing whether these control other Th2 cell-dependent processes such as worm expulsion, allergic asthma, and dermatitis.