Dramatically reduced surface expression of NK cell receptor KIR2DS3 is attributed to multiple residues throughout the molecule

Christopher VandenBussche, T. J. Mulrooney, W. R. Frazier, S. Dakshanamurthy, C. K. Hurley

Research output: Contribution to journalArticle

Abstract

Using flow cytometry, fluorescent microscopy and examination of receptor glycosylation status, we demonstrate that an entire killer cell immunoglobulin-like receptor (KIR) locus (KIR2DS3)-assumed earlier to be surface expressed-appears to have little appreciable surface expression in transfected cells. This phenotype was noted for receptors encoded by three allelic variants including the common KIR2DS3*001 allele. Comparing the surface expression of KIR2DS3 with that of the better-studied KIR2DS1 molecule in two different cell lines, mutational analysis identified multiple polymorphic amino-acid residues that significantly alter the proportion of molecules present on the cell surface. A simultaneous substitution of five residues localized to the leader peptide (residues -18 and -7), second domain (residues 123 and 150) and transmembrane region (residue 234) was required to restore KIR2DS3 to the expression level of KIR2DS1. Corresponding simultaneous substitutions of KIR2DS1 to the KIR2DS3 residues resulted in a dramatically decreased surface expression. Molecular modeling was used to predict how these substitutions contribute to this phenotype. Alterations in receptor surface expression are likely to affect the balance of immune cell signaling impacting the characteristics of the response to pathogens or malignancy.

Original languageEnglish (US)
Pages (from-to)162-173
Number of pages12
JournalGenes and Immunity
Volume10
Issue number2
DOIs
StatePublished - 2009
Externally publishedYes

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Natural Killer Cell Receptors
KIR Receptors
Phenotype
Protein Sorting Signals
Glycosylation
Microscopy
Flow Cytometry
Alleles
Amino Acids
Cell Line
Neoplasms

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Dramatically reduced surface expression of NK cell receptor KIR2DS3 is attributed to multiple residues throughout the molecule. / VandenBussche, Christopher; Mulrooney, T. J.; Frazier, W. R.; Dakshanamurthy, S.; Hurley, C. K.

In: Genes and Immunity, Vol. 10, No. 2, 2009, p. 162-173.

Research output: Contribution to journalArticle

VandenBussche, Christopher ; Mulrooney, T. J. ; Frazier, W. R. ; Dakshanamurthy, S. ; Hurley, C. K. / Dramatically reduced surface expression of NK cell receptor KIR2DS3 is attributed to multiple residues throughout the molecule. In: Genes and Immunity. 2009 ; Vol. 10, No. 2. pp. 162-173.
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