Definition of polymorphic residues on killer Ig-like receptor proteins which contribute to the HLA-C binding site
✍ Scribed by Jennifer Richardson; Hugh T. Reyburn; Isabel Luque; Mar Valés-Gómez; Jack L. Strominger
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 96 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
Killer cell immunoglobulin-like receptors (KIR) bind HLA class I proteins in an allele- and locus-specific manner. This report describes the use of transfectants expressing recombinant chimeric proteins, comprising the extracellular portions of KIR molecules and the transmembrane and cytoplasmic tails of CD3-zeta, to create an in vitro system in which signaling is readily measured and that preserves the specificity of the KIR / HLA-C interaction. The identity of the amino acid residues on the KIR molecule important for binding to the HLA protein is not well understood; although some KIR2D residues involved in HLA-C recognition have been identified, their relative importance and whether other amino acids contribute to binding was unclear. This novel system was used to study, by site-directed mutagenesis, the role of various amino acids in KIR binding to HLA-C ligand. The data presented here show that while multiple polymorphic residues contribute to the HLA-C binding site on KIR proteins, two clusters of polymorphic residues define the group allotype specificity of HLA-C binding to a KIR2D molecule.