The long term objective of this project has been the investigation of cellular alloantigen systems of the mouse with particular emphasis on the major histocompatibility gene complex (MHC). The demonstration that the MHC plays a key part in the regulation of immune responses and the observation that humans share a closely related system with mice lends clinical relevance to the investigation of the MHC. The MHC is a genetically regulated system controlled by a cluster of closely-linked genes. A goal of the project is to analyze the fine genetic structure of the MHC using genetic and immunological procedures, to identify and characterize the structural and functional properties of the component parts of the MHC and to investigate the manner in which the components of the MHC regulate immune responsiveness. Much has been learned about the mechanics of the immune response through the use of selectively bred strains of mice which are genetically closely related except for defined differences within the MHC. Other experiments are planned which involve the study of the immunogenetic properties of H-3, a minor histocompatibility locus which can evoke skin graft rejections. It is of particular interest because it may be regulated by a complex gene system. It will be investigated using immunogenetic procedures.