What is the basis for HLA-DQ associations with autoimmune disease?

The finding that diseases such as type I diabetes, coeliac disease and multiple sclerosis are HLA-DQ associated is not easily explained by a simple hypothesis of DQ-restricted, autoreactive T cells, considering the generally marginal role of DQ in restricting responses. Consequently, there have been various attempts to find a differential role for DQ, from presentation of special antigens to preferential stimulation of suppressor cells. Here, Daniel Altmann and colleagues critically assess these proposals and put forward the alternative hypothesis that the effect of DQ on disease susceptibility may result from a special role in shaping the T-cell receptor repertoire.