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

Madhan Masilamani, Sriram Narayanan, Martha Prieto, Francisco Borrego, John E. Coligan

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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.

Original languageEnglish
Pages (from-to)1019-1034
Number of pages16
Issue number6
StatePublished - Jun 2008


  • CD94/NKG2A
  • Endocytosis
  • Inhibitory receptor
  • Natural killer cells
  • Trafficking


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