The binding site of NK receptors on HLA-C molecules.
The protection of cells expressing class I HLA molecules from NK lysis is mediated by natural killer cell inhibitory receptors (NKIR). Using site-directed mutagenesis, residues on HLA-C that determine the locus specificity (alphaVal-76), allotype group specificity (a dimorphism alphaAsn-80/Lys-80), and affinity of NKIR binding (a second pair of dimorphisms, alphaAla-73, Asp-90 or alphaThr-73, Ala-90) have been identified. Thus the "footprint" of the NKIR on the alpha1 helix of the class I MHC molecule HLA-C and its associated beta strands are similar in position to the site occupied by superantigens on and behind the alpha1 helix of the class II MHC molecule HLA-DR1, but further toward its C-terminus. The intermediate affinity binding of NKIR to HLA-C, determined by alpha73 and alpha90, has an essential role in preventing cross-reactivity and ensuring the availability of NK cells for immunosurveillance; low affinity and high affinity mutants are both physiologically impaired.
Mandelboim
O
O
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 01238, USA.
Reyburn
H T
HT
Sheu
E G
EG
Vales-Gomez
M
M
Davis
D M
DM
Pazmany
L
L
Strominger
J L
JL
D000328:Adult; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D015236:HLA-C Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D011971:Receptors, Immunologic / Q000032:analysis / Q000235:genetics* / Q000276:immunology*; D054340:Receptors, KIR
D015236:HLA-C Antigens; D011971:Receptors, Immunologic; D054340:Receptors, KIR