HLA-DM sensitivity is mediated via interaction with HLA-DRα. The effect of point mutation E40K in DRα (DRA mut) versus wild-type DRα (DRA wt) was tested on the presentation of DM-resistant antigens MTHFD1 and PTK2B (top) as well as DM-sensitive antigens LY75 and MR1 (bottom). HeLa variants were transduced with the genes for DRA wt or DRA mut in combination with the appropriate DRB chains and tested for T-cell recognition after exogenous loading of the indicated recombinant proteins. Mean ± SD release of IFN-γ after coincubation with the specific T-cell clones is depicted.