Work

A disulfide-linked natural killer cell receptor dimer has higher affinity for HLA-C than wild-type monomer

Year: 2000

Type: article

Abstract: 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.

Source: European Journal of Immunology

DOI: 10.1002/1521-4141(200009)30:9<2692::aid-immu2692>3.0.co;2-0

Authors: Qing R. Fan, Eric O. Long, Don C. Wiley

Institutions: Howard Hughes Medical Institute, Harvard University, National Institute of Allergy and Infectious Diseases

Language: English

Topic: Immune Cell Function and Interaction

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Science Foundation, Howard Hughes Medical Institute, National Institutes of Health