A disulfide-linked natural killer cell receptor dimer has higher affinity for HLA-C than wild-type monomer.
Inhibitory receptors on the surface of natural killer (NK) cells recognize specific MHC class I molecules on target cells and prevent the target cell lysis by NK cells. The killer cell immunoglobulin-related receptors (KIR), KIR2D, found in human, specifically interact with polymorphic HLA-C molecules. The crystal structure of the inhibitory receptor, KIR2DL1, revealed a relationship to the hematopoietic receptor family, suggesting that the signaling mechanism of KIR2D molecules may resemble that of the hematopoietic receptors, and involve KIR2D dimerization. We have engineered a disulfide-linked dimer of KIR2DL1 by introducing a free cysteine at the C-terminal stem region of the receptor. The disulfide-linked KIR2DL1 dimer binds to HLA-Cw4 at a molar ratio of one dimer to one HLA-Cw4 molecule. Furthermore, the covalently-linked KIR2DL1 dimer binds more tightly to HLA-Cw4 than the wild-type monomer, suggesting the occurrence of a second binding event that increases the overall affinity of KIR dimer for HLA-C.
Fan
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Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
Long
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Wiley
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D019281:Dimerization; D004220:Disulfides / Q000378:metabolism; D015236:HLA-C Antigens / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism*; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D013329:Structure-Activity Relationship
D004220:Disulfides; D015236:HLA-C Antigens; C039966:HLA-C*04 antigen; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1