Uncommon endocytic and trafficking pathway of the natural killer cell CD94/NKG2A inhibitory receptor

Traffic. 2008 Jun;9(6):1019-34. doi: 10.1111/j.1600-0854.2008.00738.x. Epub 2008 Mar 19.

Abstract

The CD94/NKG2A inhibitory receptor, expressed by natural killer and T cells, is constantly exposed to its HLA-E ligand expressed by surrounding cells. Ligand exposure often induces receptor downregulation. For CD94/NKG2A, this could potentiate activation receptor(s) induced responses to normal bystander cells. We investigated CD94/NKG2A endocytosis and found that it occurs by an amiloride-sensitive, Rac1-dependent macropinocytic-like process; however, it does not require clathrin, dynamin, ADP ribosylation factor-6, phosphoinositide-3 kinase or the actin cytoskeleton. Once endocytosed, CD94/NKG2A traffics to early endosomal antigen 1(+), Rab5(+) early endosomes. It does appear in Rab4(+) early/sorting endosome, but, in the time period examined, fails to reach Rab11(+) recycling or Rab7(+) late endosomes or lysosome-associated membrane protein-1(+) lysosomes. These results indicate that CD94/NKG2A utilizes a previously undescribed endocytic mechanism coupled with an abbreviated trafficking pattern, perhaps to insure surface expression.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • ADP-Ribosylation Factor 6
  • Dynamins / antagonists & inhibitors
  • Endocytosis*
  • Fluorescent Antibody Technique, Indirect
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Hydrazones / pharmacology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D / immunology
  • NK Cell Lectin-Like Receptor Subfamily D / metabolism*
  • Protein Transport
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Receptors, Natural Killer Cell

Substances

  • ADP-Ribosylation Factor 6
  • Hydrazones
  • KLRC1 protein, human
  • N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • RNA, Small Interfering
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Green Fluorescent Proteins
  • ARF6 protein, human
  • Dynamins