GENETIC-MAPPING OF A MURINE LOCUS CONTROLLING DEVELOPMENT OF T-HELPER-1 T-HELPER-2 TYPE RESPONSES

Genetic background of the T cell can influence T helper (Th) phenotype development, with some murine strains (e.g., B10.D2) favoring Th1 dev elopment and others (e.g., BALB/c) favoring Th2 development. Recently we found that B10.D2 exhibit an intrinsically greater capacity to main tain interleukin 12 (IL-12) responsiveness under neutral conditions in vitro compared with BALB/c T cells, allowing for prolonged capacity t o undergo IL-12-induced Th1 development. To begin identification of th e loci controlling this genetic effect, we used a T cell antigen recep tor-transgenic system for in vitro analysis of intercrosses between BA LB/c and B10.D2 mice and have identified a locus on murine chromosome 11 that controls the maintenance of IL-12 responsiveness, and therefor e the subsequent Th1/Th2 response. This chromosomal region is syntenic with a locus on human chromosome 5q31.1 shown to be associated with e levated serum IgE levels, suggesting that genetic control of Th1/Th2 d ifferentiation in mouse, and of atopy development in humans, may be ex pressed through similar mechanisms.