A humanized model of experimental autoimmune uveitis in HLA class II transgenic mice
| Autor: | J. Hugh McDowell, Paul A. Hargrave, W. Clay Smith, Giuseppina Pennesi, Zaruhi Karabekian, Chella S. David, Mary J. Mattapallil, Larry A. Donoso, Phyllis B. Silver, Barbara Wiggert, Shu Hui Sun, Dody Avichezer, Chi-Chao Chan, Rachel R. Caspi |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Molecular Sequence Data
Antigen presentation Epitopes T-Lymphocyte Mice Transgenic Lymphocyte proliferation Human leukocyte antigen Biology Major histocompatibility complex Article Epitope Autoimmune Diseases Uveitis Mice HLA-DR3 Antigen Immune system Antigen immune system diseases medicine Animals Humans Amino Acid Sequence Eye Proteins Antigen Presentation Arrestin Histocompatibility Antigens Class II General Medicine medicine.disease eye diseases Mice Inbred C57BL Retinol-Binding Proteins Disease Models Animal Immunology biology.protein sense organs |
| Zdroj: | Journal of Clinical Investigation. 111:1171-1180 |
| ISSN: | 0021-9738 |
| Popis: | Experimental autoimmune uveitis (EAU) is a disease of the neural retina induced by immunization with retinal antigens, such as interphotoreceptor retinoid-binding protein (IRBP) and arrestin (retinal soluble antigen, S-Ag). EAU serves as a model for human autoimmune uveitic diseases associated with major histocompatibility complex (HLA) genes, in which patients exhibit immunological responses to retinal antigens. Here we report the development of a humanized EAU model in HLA transgenic (TG) mice. HLA-DR3, -DR4, -DQ6, and -DQ8 TG mice were susceptible to IRBP-induced EAU. Importantly, HLA-DR3 TG mice developed severe EAU with S-Ag, to which wild-type mice are highly resistant. Lymphocyte proliferation was blocked by anti-HLA antibodies, confirming that antigen is functionally presented by the human MHC molecules. Disease could be transferred by immune cells with a Th1-like cytokine profile. Antigen-specific T cell repertoire, as manifested by responses to overlapping peptides derived from S-Ag or IRBP, differed from that of wild-type mice. Interestingly, DR3 TG mice, but not wild-type mice, recognized an immunodominant S-Ag epitope between residues 291 and 310 that overlaps with a region of S-Ag recognized by uveitis patients. Thus, EAU in HLA TG mice offers a new model of uveitis that should represent human disease more faithfully than currently existing models. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|