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 molecul...
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Veröffentlicht in: | European journal of immunology 2000-09, Vol.30 (9), p.2692-2697 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0014-2980 1521-4141 |
DOI: | 10.1002/1521-4141(200009)30:9<2692::AID-IMMU2692>3.0.CO;2-0 |