Characterization of HLA DR2 and DQ8 transgenic mouse with a new engineered mouse class II deletion, which lacks all endogenous class II genes

Human autoimmune diseases are a class of complex immune system disorders characterized by loss of tolerance to self-antigens. HLA class 11 molecules play a central role in the initiation, propagation and prolongation of the disease process. HLA class 11 transgenic mice with mouse endogenous class 11 gene Ab knockout were used successfully in several mouse models for human autoimmune diseases, such as IDDM, SLE and EAE in our Lab. However, these mice carry the functional mouse Eb gene from the Abeta(0/0) construct and could express Ebeta/DRa(Ea) molecules and shape the T cell repertoire in these mice. Recently, we have obtained the new MHCIIDelta/Delta mice that are devoid of all endogenous conventional mouse MHC class 11 genes. When these mice are mated with our HLA class 11 transgenic mice, only human class 11 genes are expressed. The DR and DQ molecules expressed in these mice shape the T cell repertoire and regulate the immune response. Therefore, this new class of HLA transgenic mice is the first to be completely "humanized" in their MHC class 11 genes and will be an invaluable mouse model for human MHC class 11 associated autoimmune diseases. (C) 2003 Published by Elsevier Ltd.