STRUCTURAL FEATURES IMPOSE TIGHT PEPTIDE BINDING-SPECIFICITY IN THE NONCLASSICAL MHC MOLECULE HLA-E

The crystal structure of the nonclassical human class Ib MHC molecule HLA-E has been determined in complex with a prototypic ligand, the non amer peptide (VMAPRTVLL), derived from the highly conserved residues 3 -11 of the human MHC class la leader sequence. The mode of peptide bin ding retains some of the standard features observed in MHC class la co mplexes, but novel features imply that HLA-E has evolved to mediate sp ecific binding to a tightly defined set of almost identical hydrophobi c peptides from the highly conserved class I leader sequences. These m olecular adaptations make HLA-E a rigorous checkpoint at the cell surf ace reporting on the integrity of the antigen processing pathway to CD 94/NKG2 receptor-bearing natural killer cells.