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-Ag7, 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-Ag7 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.
Hidde L. Ploegh
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