Hierarchy of the human natural killer cell response is determined by class and quantity of inhibitory receptors for self-HLA-B and HLA-C ligands Journal Article
| Authors: | Yu, J.; Heller, G.; Chewning, J.; Kim, S.; Yokoyama, W. M.; Hsu, K. C. |
| Article Title: | Hierarchy of the human natural killer cell response is determined by class and quantity of inhibitory receptors for self-HLA-B and HLA-C ligands |
| Abstract: | The interaction of NK inhibitory killer Ig-like receptors (KIRs) with self-MHC class I molecules mediates NK tolerance to self while conferring functional competence. Through single-cell analysis of intracellular IFN-γ production and NK clone cytotoxicity we evaluated the resting NK repertoire, analyzing the responsiveness of NK subgroups expressing discrete combinations of non-KIR and KIR class I-specific receptors. CD94:NKG2A and Ig-like transcript 2 (ILT2)-expressing cells have a modest response to class I-negative target cells, but NK cells expressing inhibitory KIRs to self-MHC class I ligands, both HLA-B and HLA-C ligands, achieve significantly higher effector capacity. There is a dose effect of KIR for self-MHC on effector capacity, but even in the most highly responsive NK cells expressing more than one inhibitory KIR for self-MHC the presentation of only one cognate MHC ligand is sufficient to abolish response. Among KIR+ cells there is preferential expression for inhibitory KIR for self-MHC. The likelihood of KIR expression is influenced by whether other KIRs are already expressed on the same cell, supporting a model of serial acquisition of KIR expression. These findings define how inhibitory receptor and autologous HLA interactions impact single-cell function and demonstrate that the resting human NK repertoire is highly attuned but variegated in response. These findings have important implications for the resting NK response to viral pathogens and malignancy, for donor selection in allogeneic hemopoietic cell transplantation, and for models of NK tolerance. Copyright © 2007 by The American Association of Immunologists, Inc. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; genetics; sensitivity and specificity; metabolism; cell function; interleukin 2; classification; cell line; protein interaction; cytotoxicity; molecular cloning; immunology; hla-c antigens; ligand; autoantigen; autoantigens; ligands; natural killer cell; killer cells, natural; killer cell immunoglobulin like receptor; receptors, kir; hla b antigen; hla c antigen; hla-b antigens; cell transplantation; interleukin-2; receptors, immunologic; immunoglobulin receptor; cd94 antigen; natural killer cell activating receptors; antigens, cd94 |
| Journal Title: | Journal of Immunology |
| Volume: | 179 |
| Issue: | 9 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2007-11-01 |
| Start Page: | 5977 |
| End Page: | 5989 |
| Language: | English |
| PUBMED: | 17947671 |
| PROVIDER: | scopus |
| DOI: | 10.4049/jimmunol.179.9.5977 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 58" - "Export Date: 17 November 2011" - "CODEN: JOIMA" - "Source: Scopus" |
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