Dataset Information

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

ACCESS DATA

Publications

Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells.

Ooi Joshua D JD Petersen Jan J Tan Yu H YH Huynh Megan M Willett Zoe J ZJ Ramarathinam Sri H SH Eggenhuizen Peter J PJ Loh Khai L KL Watson Katherine A KA Gan Poh Y PY Alikhan Maliha A MA Dudek Nadine L NL Handel Andreas A Hudson Billy G BG Fugger Lars L Power David A DA Holt Stephen G SG Coates P Toby PT Gregersen Jon W JW Purcell Anthony W AW Holdsworth Stephen R SR La Gruta Nicole L NL Reid Hugh H HH Rossjohn Jamie J Kitching A Richard AR

Nature 20170503 7653

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]

PMID: 28467828

Similar Datasets

Project description:The presentation of virus-derived peptides by HLA class I molecules on the surface of an infected cell and the recognition of these HLA-peptide complexes by, and subsequent activation of, CD8+ cytotoxic T cells provides an important mechanism for immune protection against viruses. Recent advances in proteogenomics have allowed researchers to discover a growing number of unique HLA-restricted viral peptides, resulting in a rapidly expanding repertoire of targets for immunotherapeutics (i.e. bispecific antibodies, engineered T-cell receptors (TCRs), chimeric antigen receptor T-cells (CAR-Ts)) to infected tissues. However, genomic variability between viral strains, such as Hepatitis-B virus (HBV), in combination with differences in patient HLA alleles, make it difficult to develop therapeutics against these targets. To address this challenge, we developed a novel proteogenomics approach for generating patient-specific databases that enable the identification of viral peptides based on the viral transcriptomes sequenced from individual patient liver samples. We also utilized DNA sequencing of patient samples to identify HLA genotypes and assist in target selection. Liver samples from 48 HBV infected patients, primarily from Asia, were examined to reconstruct patient-specific HBV genomes, identify regions within the human chromosomes targeted by HBV integrations and obtain a comprehensive view of HBV peptide epitopes using our HLA class-I (HLA-I) immunopeptidomics discovery platform. Two previously reported HLA associated HBV-derived peptides, HLA-A02 binder FLLTRILTI (S194-202) from the large surface antigen and HLA-A11 binder STLPETTVVRR (C141-151) from the capsid protein were validated by our discovery platform, but both were detected at a very low frequencies. In addition, we identified and validated, using heavy peptide analogues, novel strain-specific HBV-HLA associated peptides, such as GSLPQEHIVQK (P606-616) and variants. Overall, our novel approach can guide the development of bispecific antibody, TCR-T, or CAR-T based therapeutics for the treatment of HBV-related HCC and inform vaccine development.

Dataset Information

HLA DR1 and DR15 ligands isolated from transgenic mice

Publications

Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure