Proteomics

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HLA DR1 and DR15 ligands isolated from transgenic mice


ABSTRACT: Dominant protection from HLA-associated autoimmune disease is conferred by antigen specific regulatory T cells. Susceptibility and protection against human T cell mediated autoimmune diseases, including type I diabetes, multiple sclerosis and Goodpasture’s disease, is associated with particular Human Leukocyte Antigen (HLA) alleles. However, the mechanisms underpinning such HLA-mediated effects on self-tolerance, and the interplay with the responding autoreactive T cell repertoires, remain unclear. To address this central question, we investigated the molecular mechanism of Goodpasture’s disease, an HLA-linked autoimmune renal disorder characterized by an immunodominant CD4+ T cell self-epitope derived from the alpha3 chain of Type IV collagen (alpha3135-145). While HLA-DR15 confers a markedly increased disease risk (odds ratio 8.5), the protective HLA-DR1 allele (odds ratio 0.3) is dominantly protective in trans with HLA-DR15 (odds ratio 1.4). This dataset contains RAW data and database search results identifying the HLA-bound peptides from transgenic mice expressing either human HLA-DR1 or -DR15.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Spleen, Lymph Node

SUBMITTER: Sri Ramarathinam  

LAB HEAD: Anthony W Purcell

PROVIDER: PXD005935 | Pride | 2017-05-04

REPOSITORIES: Pride

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Susceptibility and protection against human autoimmune diseases, including type I diabetes, multiple sclerosis, and Goodpasture disease, is associated with particular human leukocyte antigen (HLA) alleles. However, the mechanisms underpinning such HLA-mediated effects on self-tolerance remain unclear. Here we investigate the molecular mechanism of Goodpasture disease, an HLA-linked autoimmune renal disorder characterized by an immunodominant CD4<sup>+</sup> T-cell self-epitope derived from the α  ...[more]

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