T cell targeted immunotherapy for autoimmune disease

Lee, Erica; Sinha, Animesh A.

doi:10.1080/08916930500418136

Cited by 6 publications

(5 citation statements)

References 167 publications

(161 reference statements)

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“…18 (Dsg3 78–94, 96–112, 161–177, 189–205, 190–204, 205–221, 206–220, 210–226, 250–266, 251–265, 342–356, 342–358, 376–392, 380–396, 483–499, 786–800, 810–824, 963–977) were predicted to bind to both DRB1*0402 and DQB1*0503. These observations are of particular interest in that both DRB1*0402 and DQB1*0503 are strongly linked to PV [39,40], indicating that common or overlapping dominant epitopes may be responsible for inducing disease in DR4 and DR6 patients respectively.…”

Section: Resultsmentioning

confidence: 99%

Prediction of desmoglein-3 peptides reveals multiple shared T-cell epitopes in HLA DR4- and DR6- associated Pemphigus vulgaris

et al. 2006

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Background: Pemphigus vulgaris (PV) is a severe autoimmune blistering skin disorder that is strongly associated with major histocompatibility complex class II alleles DRB1*0402 and DQB1*0503. The target antigen of PV, desmoglein 3 (Dsg3), is crucial for initiating T-cell response in early disease. Although a number of T-cell specificities within Dsg3 have been reported, the number is limited and the role of T-cells in the pathogenesis of PV remains poorly understood. We report here a structure-based model for the prediction of peptide binding to DRB1*0402 and DQB1*0503. The scoring functions were rigorously trained, tested and validated using experimentally verified peptide sequences.

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Section: Resultsmentioning

confidence: 99%

Prediction of desmoglein-3 peptides reveals multiple shared T-cell epitopes in HLA DR4- and DR6- associated Pemphigus vulgaris

et al. 2006

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“…In the clinic, T cell-directed therapies for autoimmunity have a long and complicated history (39). As an example, alemtuzumab (anti-CD52) causes profound depletion of peripheral T cells in humans but has not been efficacious in the treatment of autoimmune diseases such as RA and SLE.…”

Section: Discussionmentioning

confidence: 99%

The Bcl-2 Family Antagonist ABT-737 Significantly Inhibits Multiple Animal Models of Autoimmunity

Bardwell

McCarthy

et al. 2009

The Journal of Immunology

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The Bcl-2 family of proteins plays a critical role in controlling immune responses by regulating the expansion and contraction of activated lymphocyte clones by apoptosis. ABT-737, which was originally developed for oncology, is a potent inhibitor of Bcl-2, Bcl-xL, and Bcl-w protein function. There is evidence that Bcl-2–associated dysregulation of lymphocyte apoptosis may contribute to the pathogenesis of autoimmunity and lead to the development of autoimmune diseases. In this study, we report that ABT-737 treatment resulted in potent inhibition of lymphocyte proliferation as measured by in vitro mitogenic or ex vivo Ag-specific stimulation. More importantly, ABT-737 significantly reduced disease severity in tissue-specific and systemic animal models of autoimmunity. Bcl-2 family antagonism by ABT-737 was efficacious in treating animal models of arthritis and lupus. Our results suggest that treatment with a Bcl-2 family antagonist represents a novel and potentially attractive therapeutic approach for the clinical treatment of autoimmunity.

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“…However, current treatments of autoimmune diseases are not curative and induce general immunosuppression which is associated with serious infection and other adverse outcomes (2). Therefore, it is necessary to develop new therapeutics in order to selectively suppress autoreactive immune cells, including B cells, CD4 + T cells, and CD8 + T cells.…”

Section: Introductionmentioning

confidence: 99%

Priming of Autoreactive CD8⁺T Cells Is Inhibited by Immunogenic Peptides Which Are Competitive for Major Histocompatibility Complex Class I Binding

et al. 2013

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In the present study, we investigated if priming of autoreactive CD8+ T cells would be inhibited by competitive peptides for major histocompatibility complex (MHC) class I binding. We used a mouse model of vitiligo which is induced by immunization of Kb-binding tyrosinase-related protein 2 (TRP2)-180 peptide. Competitive peptides for Kb binding inhibited IFN-γ production and proliferation of TRP2-180-specific CD8+ T cells upon ex vivo peptide restimulation, while other MHC class I-binding peptides did not. In mice, the capability of inhibition was influenced by T-cell immunogenicity of the competitive peptides. The competitive peptide with a high T-cell immunogenicity efficiently inhibited priming of TRP2-180-specific CD8+ T cells in vivo, whereas the competitive peptide with a low T-cell immunogenicity did not. Taken together, the inhibition of priming of autoreactive CD8+ T cells depends on not only competition of peptides for MHC class I binding but also competitive peptide-specific CD8+ T cells, suggesting that clonal expansion of autoreactive T cells would be affected by expansion of competitive peptide-specific T cells. This result provides new insights into the development of competitive peptides-based therapy for the treatment of autoimmune diseases.

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T cell targeted immunotherapy for autoimmune disease

Cited by 6 publications

References 167 publications

Prediction of desmoglein-3 peptides reveals multiple shared T-cell epitopes in HLA DR4- and DR6- associated Pemphigus vulgaris

Prediction of desmoglein-3 peptides reveals multiple shared T-cell epitopes in HLA DR4- and DR6- associated Pemphigus vulgaris

The Bcl-2 Family Antagonist ABT-737 Significantly Inhibits Multiple Animal Models of Autoimmunity

Priming of Autoreactive CD8⁺T Cells Is Inhibited by Immunogenic Peptides Which Are Competitive for Major Histocompatibility Complex Class I Binding

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T cell targeted immunotherapy for autoimmune disease

Cited by 6 publications

References 167 publications

Prediction of desmoglein-3 peptides reveals multiple shared T-cell epitopes in HLA DR4- and DR6- associated Pemphigus vulgaris

Prediction of desmoglein-3 peptides reveals multiple shared T-cell epitopes in HLA DR4- and DR6- associated Pemphigus vulgaris

The Bcl-2 Family Antagonist ABT-737 Significantly Inhibits Multiple Animal Models of Autoimmunity

Priming of Autoreactive CD8+T Cells Is Inhibited by Immunogenic Peptides Which Are Competitive for Major Histocompatibility Complex Class I Binding

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Priming of Autoreactive CD8⁺T Cells Is Inhibited by Immunogenic Peptides Which Are Competitive for Major Histocompatibility Complex Class I Binding