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 II molecules play a central role in the initiation, propagation and prolongation of the disease process. HLA class II transgenic mice with mouse endogenous class II 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/DRalpha(Ealpha) molecules and shape the T cell repertoire in these mice. Recently, we have obtained the new MHCII(Delta/Delta) mice that are devoid of all endogenous conventional mouse MHC class II genes. When these mice are mated with our HLA class II transgenic mice, only human class II 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 II genes and will be an invaluable mouse model for human MHC class II associated autoimmune diseases.
Department of Immunology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
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Cheng
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Smart
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Hanson
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David
D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000494:pharmacology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D018920:Coculture Techniques; D003094:Collagen / Q000737:chemistry; D004768:Enterotoxins / Q000494:pharmacology; D005434:Flow Cytometry; D017353:Gene Deletion; D005802:Genes, MHC Class II / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015802:HLA-DR2 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology; D014611:Vaccination
D000942:Antigens, Bacterial; D004768:Enterotoxins; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D015802:HLA-DR2 Antigen; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C031818:enterotoxin B, staphylococcal; D003094:Collagen; D017493:Leukocyte Common Antigens