Reading Summary, Week 6

HLA-DQ gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus

John A. Todd, John I. Bell, & Hugh McDevitt

In studying polygenic human diseases, specifically autoimmune disease, research has found a higher frequency of lymphoid cell-surface proteins encoded in the HLA-D regions of the MHC (class II antigens). These HLA class II antigens are expressed on the surface of B cells and antigen-presenting cells; interaction with the T-cell receptor, antigenic peptide, and the class II molecule then leads to an immune response to the antigen. From this, we learn that the immune responsive in part determined by polymorphic amino acids present in the class II molecules.

Type I Diabetes is the result of the destruction of insulin producing islet cells of the pancreas, and some have argued that this disease develops from an autoimmune response to an islet antigen and is mediated by T-cells. It is estimated that the HLA-D region contributes over 50% of the heritability of this polygenic disease.

This study sequenced polymorphic class II gene products from three patients with Type I diabetes against several control patients.

The major findings of the article were that there were no unique class II sequences found only in the Type I diabetic patients, that the DQ-B-chain amino-acid sequence is correlated with predisposition to Type I diabetes, and that this susceptibility is largely dependent on amino-acid residues (position 57). The authors argue that DQ-B allelic polymorphisms at position 57 determine the specificity and extent of the autoimmune response against the islet cell antigens (with T cell help or suppression).