Structural features impose tight peptide binding specificity in the nonclassical MHC molecule HLA-E.
The crystal structure of the nonclassical human class lb MHC molecule HLA-E has been determined in complex with a prototypic ligand, the nonamer peptide (VMAPRTVLL), derived from the highly conserved residues 3-11 of the human MHC class la leader sequence. The mode of peptide binding retains some of the standard features observed in MHC class la complexes, but novel features imply that HLA-E has evolved to mediate specific binding to a tightly defined set of almost identical hydrophobic peptides from the highly conserved class l leader sequences. These molecular adaptations make HLA-E a rigorous checkpoint at the cell surface reporting on the integrity of the antigen processing pathway to CD94/NKG2 receptor-bearing natural killer cells.
O'Callaghan
C A
CA
Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom.
Tormo
J
J
Willcox
B E
BE
Braud
V M
VM
Jakobsen
B K
BK
Stuart
D I
DI
McMichael
A J
AJ
Bell
J I
JI
Jones
E Y
EY
D003461:Crystallography; D006680:HLA Antigens / Q000737:chemistry* / Q000378:metabolism*; D015795:HLA-B8 Antigen / Q000737:chemistry; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D000097625:HLA-E Antigens
D006680:HLA Antigens; D015795:HLA-B8 Antigen; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D000097625:HLA-E Antigens