Biomedical subjects

H Drakesmith

Publications and source records attributed to H Drakesmith.

3 recordsLinked to original sources

PubMed2000

The structure and function of HFE.

The iron overload disease hereditary haemochromatosis (HH) occurs in about 1 in 300 Caucasians; the protein mutated in this disorder is termed HFE.(1) HFE is homologous to major histocompatibility complex (MHC) class I proteins, but unlike MHC class I molecules, HFE does not present peptides to T cells.(2) The transferrin receptor (TfR) is a ligand for HFE, and the crystal structure of the HFE-TfR complex has been determined.(3) The many interesting features of this structure illustrate the diverse roles of the MHC fold in nature and clarify how HFE affects TfR function. Whether the interaction between HFE and TfR explains the pathogenesis of HH is not so clear.

HLA Antigens↗

PubMed2000

How can dendritic cells cause autoimmune disease?

Immune responses against foreign antigens are initiated and controlled by dendritic cells (DCs). Accumulating evidence suggests that autoimmunity, involving T cells directed against self, can also be primed by DCs. We propose that DCs could induce autoimmunity following their differentiation by certain cytokines, or because of intrinsic defects in genes controlling DC function. Both processes result in DCs that behave deviantly.

Animals↗

PubMed1998

In vivo priming of T cells against cryptic determinants by dendritic cells exposed to interleukin 6 and native antigen.

T cells recognizing poorly displayed self determinants escape tolerance mechanisms and persist in the adult repertoire. The process by which these T cells are primed is not clear, but once activated, they can cause autoimmunity. Here, we show that dendritic cells treated with interleukin 6 (IL-6) process and present determinants from a model native antigen in a qualitatively altered hierarchy, activating T cells in vitro and in vivo against determinants that were previously cryptic because of poor display. IL-6 does not induce conventional maturation of dendritic cells but alters the pH of peripheral, early endosomal compartments and renders the cells more susceptible to killing by chloroquine. Acidification of endosomes by ouabain mimics the effect of IL-6 and allows processing of the same cryptic determinant. These results suggest that cytokines such as IL-6 could initiate and help to propagate an autoimmune disease process by differentiating dendritic cells into a state distinct from that induced by normal maturation.

Animals↗