The binding site of NK receptors on HLA-C molecules

Ofer Mandelboim*, Hugh T. Reyburn, Eric G. Sheu, Mar Valés-Gómez, Daniel M. Davis, Laszlo Pazmany, Jack L. Strominger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

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 (αVal-76), allotype group specificity (a dimorphism αAsn-80/Lys-80), and affinity of NKIR binding (a second pair of dimorphisms, αAla-73, Asp-90 or αThr-73, Ala-90) have been identified. Thus the 'footprint' of the NKIR on the α1 helix of the class I MHC molecule HLA-C and its associated β strands are similar in position to the site occupied by superantigens on and behind the α1 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 α73 and α90, 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.

Original languageAmerican English
Pages (from-to)341-350
Number of pages10
JournalImmunity
Volume6
Issue number3
DOIs
StatePublished - Mar 1997
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grant CA-47554. O. M. is an EMBO Fellow and a Fulbright scholar. H. T. R. holds a Wellcome Trust International Prize Travelling Research Fellowship. L. P. is a recipient of an Arthritis Foundation postdoctoral fellowship.

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