Abstract

Human CD94/NKG2A is an inhibitory receptor that recognizes HLA-E and is expressed by NK cells and a subset of T cells. We have analyzed the cellular trafficking of the CD94/NKG2A receptor using the NKL cell line and peripheral blood NK cells. Flow cytometric, confocal microscopic, and biochemical analyses show that CD94/NKG2A continuously recycles in an active process that requires the cytoskeleton between the cell surface and intracellular compartments that are distinquishable from recycling compartments used by well-characterized receptors, such as the transferrin receptor (CD71). CD94/NKG2A, an inhibitory receptor, traffics differently from the closely related CD94/NKG2C molecule, an activating receptor. Using transfection/expression analyses of wild-type and mutant CD94/NKG2A molecules in the HLA-E negative rat basophilic cell line RBL-2H3, we demonstrate that CD94/NKG2A internalization is independent of ligand cross-linking or the presence of functional immunoreceptor tyrosine-based inhibition motifs. Thus, the mechanisms that control cell surface homeostasis of CD94/NKG2A are independent of functional signaling.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000543-16
Application #
6808252
Study Section
(LAD)
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2003
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Burgess, Steven J; Marusina, Alina I; Pathmanathan, Ishani et al. (2006) IL-21 down-regulates NKG2D/DAP10 expression on human NK and CD8+ T cells. J Immunol 176:1490-7
Lieto, L D; Maasho, K; West, D et al. (2006) The human CD94 gene encodes multiple, expressible transcripts including a new partner of NKG2A/B. Genes Immun 7:36-43
Marusina, Alina I; Kim, Dae-Ki; Lieto, Louis D et al. (2005) GATA-3 is an important transcription factor for regulating human NKG2A gene expression. J Immunol 174:2152-9
Borrego, Francisco; Masilamani, Madhan; Kabat, Juraj et al. (2005) The cell biology of the human natural killer cell CD94/NKG2A inhibitory receptor. Mol Immunol 42:485-8
Kim, Dae-Ki; Kabat, Juraj; Borrego, Francisco et al. (2004) Human NKG2F is expressed and can associate with DAP12. Mol Immunol 41:53-62
Sanni, Tolib B; Masilamani, Madhan; Kabat, Juraj et al. (2004) Exclusion of lipid rafts and decreased mobility of CD94/NKG2A receptors at the inhibitory NK cell synapse. Mol Biol Cell 15:3210-23
Maasho, Kerima; Marusina, Alina; Reynolds, Nicole M et al. (2004) Efficient gene transfer into the human natural killer cell line, NKL, using the Amaxa nucleofection system. J Immunol Methods 284:133-40
Lieto, Louis D; Borrego, Francisco; You, Chi-Hyun et al. (2003) Human CD94 gene expression: dual promoters differing in responsiveness to IL-2 or IL-15. J Immunol 171:5277-86
Borrego, Francisco; Kabat, Juraj; Sanni, Tolib B et al. (2002) NK cell CD94/NKG2A inhibitory receptors are internalized and recycle independently of inhibitory signaling processes. J Immunol 169:6102-11
Kabat, Juraj; Borrego, Francisco; Brooks, Andrew et al. (2002) Role that each NKG2A immunoreceptor tyrosine-based inhibitory motif plays in mediating the human CD94/NKG2A inhibitory signal. J Immunol 169:1948-58

Showing the most recent 10 out of 11 publications