HLA DR1 and DR15 ligands isolated from transgenic mice

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.