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Related Experiment Videos

KIR2DL4 (CD158d) genotype influences expression and function in NK cells.

Jodie P Goodridge1, Campbell S Witt, Frank T Christiansen

  • 1Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, Australia.

Journal of Immunology (Baltimore, Md. : 1950)
|August 7, 2003
PubMed
Summary

Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4) expression and function depend on its genetic variants. The 10A allele enables KIR2DL4 surface expression and activation, unlike the 9A allele.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • The expression and function of the NK cell receptor KIR2DL4 are debated.
  • Two common alleles of KIR2DL4, 10A and 9A, differ in their transmembrane exon sequence.
  • These allelic differences may impact KIR2DL4 expression and function.

Purpose of the Study:

  • To investigate the impact of KIR2DL4 10A and 9A alleles on receptor expression and function.
  • To clarify the controversial aspects of KIR2DL4 biology.

Main Methods:

  • Transfection experiments using cDNA from 10A and 9A alleles.
  • Analysis of KIR2DL4 expression on peripheral blood NK cells.
  • Functional assays (redirected lysis) using cultured NK cells.

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Main Results:

  • The 10A allele, but not the 9A allele, resulted in significant membrane expression of KIR2DL4.
  • Cell surface KIR2DL4 was detected on CD56(bright) NK cells from individuals with at least one 10A allele.
  • CD56(dim) NK cells expressed KIR2DL4 after in vitro culture.
  • KIR2DL4 acted as an activating receptor for NK cells with at least one 10A allele.
  • NK cells from 9A homozygous individuals showed no significant KIR2DL4 activity.

Conclusions:

  • KIR2DL4 genotype significantly influences its cell surface expression and functional activity.
  • Allelic variations in KIR2DL4 may explain previously reported discrepancies in its expression and function.