A single amino acid in the p58 killer cell inhibitory receptor controls the ability of natural killer cells to discriminate between the two groups of HLA-C allotypes.
To examine the structural basis for the specific recognition of the MHC class I allotypes HLA-Cw*0401 and HLA-Cw*0304 by the killer cell inhibitory receptors (KIR) cl42 and cl43, respectively, mutant KIR-Ig fusion proteins were tested by direct binding to cells transfected with single HLA-C alleles. The putative loop region at position 44-46 of KIR contained amino acids that were necessary for the discrimination between HLA-Cw*0401 and HLA-Cw*0304. Surprisingly, exchanging the methionine at position 44 in cl42 with the lysine at position 44 in cl43 was sufficient to switch the specificity of cl42 from HLA-Cw*0401 to HLA-Cw*0304, and vice versa. Thus, a single amino acid in the first Ig domain of these KIR determines their ability to discriminate between the two groups of HLA-C allotypes.
Winter
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Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
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D000483:Alleles; D000595:Amino Acid Sequence; D016384:Consensus Sequence; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011971:Receptors, Immunologic / Q000737:chemistry*; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D011993:Recombinant Fusion Proteins; D013329:Structure-Activity Relationship
D015236:HLA-C Antigens; C515078:KIR2DL3 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D011993:Recombinant Fusion Proteins