Spontaneous retinopathy in HLA-A29 transgenic mice

Szpak, Yann; Vieville, Jean-Claude; Tabary, Thierry; Naud, Marie‐Christine; Chopin, Martine; Edelson, C.; Cohen, Jacques H. M.; Dausset, J; Kozak, Y. de; Pla, Marika

doi:10.1073/pnas.051595998

Cited by 79 publications

(36 citation statements)

References 34 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, the recently described HLA-A29 TG mice develop spontaneous uveitis with striking histological similarity to the HLA-A29-associated disease in humans. This supports the conclusion that the HLA-A29 molecule itself participates in the pathogenesis of birdshot chorioretinopathy (41). The EAU model in HLA class II TG mice described here provides evidence in favor of an involvement of class II-restricted responses in human uveitis.…”

Section: Discussionsupporting

confidence: 72%

A humanized model of experimental autoimmune uveitis in HLA class II transgenic mice

et al. 2003

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 72%

A humanized model of experimental autoimmune uveitis in HLA class II transgenic mice

et al. 2003

View full text Add to dashboard Cite

“…A number of HLA-transgenic mouse models have been developed to study autoimmunity, and these have proven valuable in evaluating the role of individual HLA genes in disease susceptibility (8,9,(53)(54)(55). However, there are no HLA-transgenic mouse models that express multiple linked genes from common autoimmuneprone human haplotypes.…”

Section: Discussionmentioning

confidence: 99%

A 320-Kilobase Artificial Chromosome Encoding the Human HLA DR3-DQ2 MHC Haplotype Confers HLA Restriction in Transgenic Mice

Chen

Dudek

Wijburg

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

MHC class II haplotypes control the specificity of Th immune responses and susceptibility to many autoimmune diseases. Understanding the role of HLA class II haplotypes in immunity is hampered by the lack of animal models expressing these genes as authentic cis-haplotypes. In this study we describe transgenic expression of the autoimmune prone HLA DR3-DQ2 haplotype from a yeast artificial chromosome (YAC) containing an intact ∼320-kb region from HLA DRA to DQB2. In YAC-transgenic mice HLA DR and DQ gene products were expressed on B cells, macrophages, and dendritic cells, but not on T cells indicating cell-specific regulation. Positive selection of the CD4 compartment by human class II molecules was 67% efficient in YAC-homozygous mice lacking endogenous class II molecules (Aβnull/null) and expressing only murine CD4. A broad range of TCR Vβ families was used in the peripheral T cell repertoire, which was also purged of Vβ5-, Vβ11-, and Vβ12-bearing T cells by endogenous mouse mammary tumor virus-encoded superantigens. Expression of the HLA DR3-DQ2 haplotype on the Aβnull/null background was associated with normal CD8-dependent clearance of virus from influenza-infected mice and development of CD4-dependent protection from otherwise lethal infection with Salmonella typhimurium. HLA DR- and DQ-restricted T cell responses were also elicited following immunization with known T cell determinants presented by these molecules. These findings demonstrate the potential for human MHC class II haplotypes to function efficiently in transgenic mice and should provide valuable tools for developing humanized models of MHC-associated autoimmune diseases.

show abstract

“…Furthermore, TCRs specific for neoantigens typically have a much higher affinity for their cognate antigen than those specific for native antigen that escape the thymic process of central tolerance; they are thus not representative of typical autoreactive T cells. An intriguing model is spontaneous uveitis that develops between 8 and 12 months of age in HLA-A29 transgenic mice (33,34). HLA-A29 is highly associated with birdshot retinochoroidopathy in humans (Table 1).…”

Section: Figurementioning

confidence: 99%

A look at autoimmunity and inflammation in the eye

2010

View full text Add to dashboard Cite

Autoimmune and inflammatory uveitis are a group of potentially blinding intraocular inflammatory diseases that arise without a known infectious trigger and are often associated with immunological responses to unique retinal proteins. In the United States, about 10% of the cases of severe visual handicap are attributed to this group of disorders. As I discuss here, experimental models of ocular autoimmunity targeting retinal proteins have brought about a better understanding of the basic immunological mechanisms involved in the pathogenesis of uveitis and are serving as templates for the development of novel therapies.

show abstract

Spontaneous retinopathy in HLA-A29 transgenic mice

Cited by 79 publications

References 34 publications

A humanized model of experimental autoimmune uveitis in HLA class II transgenic mice

A humanized model of experimental autoimmune uveitis in HLA class II transgenic mice

A 320-Kilobase Artificial Chromosome Encoding the Human HLA DR3-DQ2 MHC Haplotype Confers HLA Restriction in Transgenic Mice

A look at autoimmunity and inflammation in the eye

Contact Info

Product

Resources

About