An N-acetylated natural ligand of human histocompatibility leukocyte antigen (HLA)-B39: Classical major histocompatibility complex class I proteins bind peptides with a blocked NH2 terminus in vivo

Sequence-independent interactions involving the free peptidic NH2 terminus are thought to be an essential feature of peptide binding to classical majo r histocompatibility complex (MHC) class I proteins. Challenging this parad igm, a natural N alpha-acetylated ligand of human histocompatibility leukoc yte antigen (HLA)-B39 was identified in this study. It matched the NH2-term inal sequence of two human helicases, was resistant to aminopeptidase M, an d was produced with high yield from a synthetic 30 mer with the sequence of the putative parental protein by the 20S proteasome. This is the first rep orted natural ligand of classical MHC class I antigens that has a blocked N H2 terminus.