A locus on chromosome 2 influences the development of acute graft-versus-host disease in a murine model

Despite contemporary typing procedures for bone marrow transplantation (BMT ), graft-versus-host disease (GVHD) continues to be a major complication of transplants performed between MHC-matched donors and recipients. Although GVHD can be alleviated by T cell depletion, this procedure increases the ri sk of graft failure and leukemic relapse and therefore is not a solution to the GVHD problem. The high degree of variation in the intensity of GVHD ob served in different patients suggests that multiple non-MHC genetic factors influence GVHD severity. We hypothesize that, in addition to minor histoco mpatibility antigen disparities, polymorphisms in genes encoding immunologi c effector molecules may be important factors influencing GVHD development, This study aims to explore this hypothesis by identifying non-MHC genes th at influence the outcome of BMT in a murine model. In this model, B10.D2 do nor leukocytes cause acute GVHD in (C57BL/6 x DBA/2)F1 (B6D2F1) recipients, whereas DBA/2 donor leukocytes do not. To date, a locus on chromosome I ha s been identified as influencing the severity of GVHD in this model, Our cu rrent study shows that a locus on chromosome 2 acts independently of the ch romosome 1 locus to also influence GVHD severity in this model, The region of chromosome 2 implicated in our study contains genes encoding beta(2)-mic roglobulin, the minor histocompatibility antigen H-3 and the pro-inflammato ry cytokine IL-1.