HLA class II transgenic mice: models of the human CD4(+) T-cell immune response

This review examines the field of current HLA class II transgenic mouse mod els and the individual approaches applied in production of these mice. The majority of these mice have been created with the objective of obtaining a disease model with clinical features mimicking human autoimmune disease. Th e development process of a different type of HLA class II transgenic mice, which are designed to function as a substitute for a normal human immune sy stem in studies of human autoantigens, is described. Several HLA-DR4 transg enic lines with normally expressed HLA-DR4 molecules have been produced. To obtain adequate positive selection of the HLA-DR4-restricted CD4(+) T-cell repertoire in these mice it is essential both to introduce a human CD4 tra nsgene, and to delete the murine major histocompatibility complex (MHC) cla ss II molecules. These HLA-DR4 transgenic mice have been used to determine the immunogenic CD4(+) T-cell epitopes of several human autoantigenic prote ins.