NK Cell Killer Ig-like Receptor Repertoire Acquisition and Maturation Are Strongly Modulated by HLA Class I Molecules
- 15 March 2014
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 192 (6), 2602-2610
- https://doi.org/10.4049/jimmunol.1302843
Abstract
The interaction between clonally distributed inhibitory receptors and their activating counterparts on NK cells and HLA class I molecules defines NK cell functions, but the role of HLA class I ligands in the acquisition of their receptors during NK development is still unclear. Although some studies demonstrated that HLA-C affects the expression of killer Ig-like receptors (KIR), other studies showed that NK cells acquire their KIR repertoire in a stochastic manner. Only when infected with human CMV is an expansion of self-specific KIR(+) NKG2C(+) NK cells detected. To gain more insight into this question, we compared the coexpression of different KIR molecules, NKG2A, CD8, and CD57, on NK cells in healthy donors and seven patients with deficient HLA class I expression due to mutations in one of the TAP genes. Our results show a correlation between the presence/absence of HLA class I molecules and the coexpression of their receptors. In an HLA class I low-expression context, an increase in KIR molecules' coexpression is detected on the NKG2A(+) CD8(+) subset. In functional assays, hyporesponsiveness was observed for TAP-deficient NK cells derived from four patients. In contrast, NK cells from patient five were functional, whereas CD107a(+) and IFN-γ(+) CD56(dim) NK cells presented a different pattern of HLA class I receptors compared with healthy donors. Taken together, our results provide strong evidence for the role of HLA class I molecules in NK cell maturation and KIR repertoire acquisition.Keywords
This publication has 31 references indexed in Scilit:
- NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRsBlood, 2013
- HLA Reduces Killer Cell Ig-like Receptor Expression Level and Frequency in a Humanized Mouse ModelThe Journal of Immunology, 2013
- Natural Killer Cell Inhibitory Receptor Expression in Humans and Mice: A Closer LookFrontiers in Immunology, 2013
- A Viral, Transporter Associated with Antigen Processing (TAP)-independent, High Affinity Ligand with Alternative Interactions Endogenously Presented by the Nonclassical Human Leukocyte Antigen E Class I MoleculeJournal of Biological Chemistry, 2012
- Human Cytomegalovirus UL40 Signal Peptide Regulates Cell Surface Expression of the NK Cell Ligands HLA-E and gpUL18The Journal of Immunology, 2012
- Innate or Adaptive Immunity? The Example of Natural Killer CellsScience, 2011
- Different Patterns of Evolution in the Centromeric and Telomeric Regions of Group A and B Haplotypes of the Human Killer Cell Ig-Like Receptor LocusPLOS ONE, 2010
- CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subsetBlood, 2010
- Regulation of NK cell responsiveness to achieve self‐tolerance and maximal responses to diseased target cellsImmunological Reviews, 2008
- Human natural killer cellsBlood, 2008