HLA class-II transgenic mice expressing class-II on subset of CD4+T cells as a model of human MS

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of CNS, believed to be mediated by T cell response directed against the myelin antigen such as proteolipid protein. Among all the genetics factors linked to MS, strongest association has been seen to MHC genes on chromosome 6. Number of HLA class II alleles such as -DR2, -DR3 and DR4 has been linked with disease; however exact role these class II molecules play in disease is not well understood due to number of factors including linkage disequilibrium. However advent of HLA transgenic mice has helped immensely in understanding the mechanism of disease pathology of number of autoimmune diseases including MS. Here we describe generation of HLA-DR3.AEo transgenic mice. These tg mice are unique in the sense that they express class II on a subset of T cells. Further these tg mice develop severe EAE and show increased demyelination in brain and spinal cord thus mimicking human MS.