An HLA-DR1 Transgene Confers Susceptibility to Collagen-induced Arthritis Elicited with Human Type II Collagen

Rosloniec, Edward F.; Brand, David; Myers, Linda K.; Whittington, Karen B.; Gumanovskaya, Marina L.; Zaller, Dennis M.; Woods, Andrea; Altmann, Daniel M.; Stuart, J.; Kang, Andrew H.

doi:10.1084/jem.185.6.1113

Cited by 207 publications

(224 citation statements)

References 41 publications

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“…Lines in which GAD65 message [42,54] HLA-DRB1*0401, HLA-DRB1*0101 Rheumatoid arthritis Type II collagen Immunization can cause HLA dependent polyarthritis Induce with whole CII or 261-273. Similar [55][56][57] findings in HLA-DR1 and HLA-DR4.…”

Section: Transgenic Expression Of Candidate Autoantigenssupporting

confidence: 61%

Transgenic models of autoimmune disease

Boyton¹,

Altmann

2002

Clinical and Experimental Immunology

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SUMMARY Transgenic and knockout mouse models have been invaluable for the elucidation of basic mechanisms in autoimmunity and have contributed new experimental models of human autoimmune diseases. Transgenic models of self tolerance have helped to change our view of this state from a process mediated purely by thymic deletion to a more complex process encompassing deletion, peripheral anergy, down‐regulation of receptors and modulation by regulatory cells. Experiments in which the genes for the candidate target antigens in autoimmune disease are over‐expressed or under‐expressed have helped to clarify the targets of attack. Several examples of T cell receptor transgenic mice have been described in which T cells carry the receptor derived from a human or mouse autoimmune T cell clone. Such mice allow the characterization of T cell specificities contributing to disease and of the additional factors and checkpoints influencing disease development. In addition, the expression of disease associated HLA alleles in ‘humanised’ transgenic lines allows the mapping of HLA‐restricted T cell epitopes and investigation of the mechanisms underlying these genetic associations. These approaches are leading to the generation of new disease models, offering hope for the design and testing of novel immunotherapeutic strategies.

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Section: Transgenic Expression Of Candidate Autoantigenssupporting

confidence: 61%

Transgenic models of autoimmune disease

Boyton¹,

Altmann

2002

Clinical and Experimental Immunology

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“…Interestingly, the human class II molecules associated with RA -DR4 and DR1 -present the same peptide, and transgenic mice expressing A q , DR4 or DR1 are susceptible to CIA [7][8][9]. The T cell response is directed towards the same immunodominant core, CII residues 260-270 [9,10].…”

Section: Introductionmentioning

confidence: 99%

The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans

et al. 2005

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Type II collagen (CII) is a target for autoreactive T cells in both rheumatoid arthritis and the murine model collagen-induced arthritis. The determinant core of CII has been identified as CII260-270, and the alteration of this T cell epitope by posttranslational modifications is known to be critical for development of arthritis in mice. Using CIIspecific T cell hybridomas we have now shown that the immunodominant T cell epitope in the normal (healthy) human and rat joint cartilage is O-glycosylated at the critical T cell receptor recognition position 264 with a mono-or di-saccharide attached to a hydroxylysine. In contrast, in the arthritic human and rat joint cartilage there are both glycosylated and non-glycosylated CII forms. Glycosylated CII from normal cartilage could not be recognized by T cells reactive to peptides having only lysine or hydroxylysine at position 264, showing that antigen-presenting cells could not degrade the O-linked carbohydrate. Thus, the variable forms of the glycosylated epitope are determined by the structures present in cartilage, and these vary during the disease course. We conclude that the chondrocyte determines the structures presented to the immune system and that these structures are different in normal versus arthritic states.

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“…induction (8), whereas both HLA-DRB*0101 (HLA-DR1 ϩ/ϩ )-transgenic and HLA-DRB*0401-transgenic mice are highly susceptible to CIA (9,10).…”

mentioning

confidence: 99%

Treatment of murine collagen‐induced arthritis by the stress protein BiP via interleukin‐4–producing regulatory T cells: A novel function for an ancient protein

Brownlie

Myers

Wooley

et al. 2006

Arthritis & Rheumatism

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Objective. Following the demonstration that the stress protein, BiP, prevented induction of collageninduced arthritis (CIA) in HLA-DRB*0101 ؉/؉ (HLA-DR1 ؉/؉ ) mice, we investigated the immunotherapeutic ability of BiP to suppress disease during the active phase of CIA in HLA-DR1 ؉/؉ and DBA/1 mice.Methods. BiP was administered either subcutaneously or intravenously to DBA/1, HLA-DR1 ؉/؉ , or interleukin-4 (IL-4)-knockout mice at the onset of arthritis. Immune cells were used in adoptive transfer studies or were restimulated in culture with BiP or type II collagen (CII). Proliferation and cytokine release were measured. In addition, serum anti-CII antibodies were measured by enzyme-linked immunosorbent assay. Disease progression was scored using a visual analog scale.Results. BiP was successful in suppressing estab-

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An HLA-DR1 Transgene Confers Susceptibility to Collagen-induced Arthritis Elicited with Human Type II Collagen

Cited by 207 publications

References 41 publications

Transgenic models of autoimmune disease

Transgenic models of autoimmune disease

The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans

Treatment of murine collagen‐induced arthritis by the stress protein BiP via interleukin‐4–producing regulatory T cells: A novel function for an ancient protein

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