Chromosomes X, 9, and the H2 locus interact epistatically to control Leishmania major infection

As in other infectious diseases, the outcome of a Leishmania major infectio n is closely tied to the T helper cell response type; progressive disease i s associated with a predominant Th2 lymphocyte response, healing with a Th1 response. In mice, susceptibility is genetically controlled, with BALB/c ( C) mice being susceptible and C57BL/6 (B) mice being resistant. Using a gen ome-wide scan on two large populations of F2 mice created from these strain s, we have shown previously that susceptibility to infection with L. major is controlled by two autosomal loci: lmr1 at the H2 locus, and lmr2 on chro mosome 9. Employing a strategy to identify loci that interact, we show here that lmr1 and lmr2 interact synergistically, and we describe a new locus l mr3, lying on the X chromosome, whose effect depends on a specific lmr1 hap lotype.