Potential natural changes and implications for a UK GDF

A period of one million years following closure has been used by RWMD when considering the post-closure safety case for a geological disposal facility (GDF). It is during this period that evolution of the near-field and local geosphere as a result of GDF construction and operation will be at its most rapid and radioactivity of the emplaced waste will be at their highest levels. Significant effort has been spent internationally on identifying the many natural processes that may affect the evolution of the geosphere over this timescale and the contribution of those processes to GDF performance. The purpose of this report is to identify which processes are relevant to geosphere evolution in this time period around a generic GDF in the UK. Previous work has identified tectonic effects, climate change effects, uplift, subsidence, volcanism and diagenesis as key concerns. The potential impact of each of these processes on a generic UK GDF, constructed according to a multiple barrier concept and sited at a depth of between 200 and 1000 m in a suitable host rock, is outlined in the following sections: tectonic related uplift and subsidence; seismicity, tectonic history and volcanism; climate change and glaciation and weathering and erosion

T cell receptor cross-reactivity between gliadin and bacterial peptides in celiac disease

Structural, biochemical and cellular analyses show that bacterial antigens can mimic gliadin epitopes involved in celiac disease being presented by HLA-DQ2.5 and recognized by T cells derived from patients.The human leukocyte antigen (HLA) locus is strongly associated with T cell-mediated autoimmune disorders. HLA-DQ2.5-mediated celiac disease (CeD) is triggered by the ingestion of gluten, although the relative roles of genetic and environmental risk factors in CeD is unclear. Here we identify microbially derived mimics of gliadin epitopes and a parental bacterial protein that is naturally processed by antigen-presenting cells and activated gliadin reactive HLA-DQ2.5-restricted T cells derived from CeD patients. Crystal structures of T cell receptors in complex with HLA-DQ2.5 bound to two distinct bacterial peptides demonstrate that molecular mimicry underpins cross-reactivity toward the gliadin epitopes. Accordingly, gliadin reactive T cells involved in CeD pathogenesis cross-react with ubiquitous bacterial peptides, thereby suggesting microbial exposure as a potential environmental factor in CeD.Transplantation and autoimmunit