A molecule's right to choose: how diabetogenic class II MHC products bind peptides

The distinction between peptides that bind to class II MHC products under laboratory conditions and those that do so physiologically is important for the prediction of antigens recognized by autoreactive T cells. In this issue of the JCI, Suri et al., using antigen-presenting cells, compared the peptides that bound to human HLA-DQ8 and those that bound to mouse I-A, both class II MHC products that predispose their carriers to type 1 diabetes. The rules of engagement for the peptide ligands of the DQ8 and I-A molecules involve similarities in their anchor residues, which mediate stable interaction with class II MHC products. The peptides identified derive from overlapping sets of self proteins.