KIR2DS1-positive NK cells mediate alloresponse against the C2 HLA-KIR ligand group in vitro Journal Article


Authors: Chewning, J. H.; Gudme, C. N.; Hsu, K. C.; Selvakumar, A.; Dupont, B.
Article Title: KIR2DS1-positive NK cells mediate alloresponse against the C2 HLA-KIR ligand group in vitro
Abstract: The inhibitory 2DL1 and activating 2DS1 killer Ig-like receptors (KIR) both have shared ligand specificity for codon sequences in the C2 group HLA-Cw Ags. In this study, we have investigated NK cell activation by allogeneic target cells expressing different combinations of the HLA-KIR ligand groups C1, C2, and Bw4. We demonstrate that fresh NK cells as well as IL-2-propagated NK cells from 2DS1-positive donors that are homozygous for the C1 ligand group are activated in vitro by B lymphoblastoid cell lines expressing the C2 group. This response is, in part, due to the absence of C1 group recognition mediated by the inhibitory receptor 2DL2/3. This "missing self" alloresponse to C2, however, is rarely observed in NK cells from donors lacking 2DS1. Even in presence of 2DS1, the NK alloresponse is dramatically reduced in donors that have C2 group as "self." Analysis of selected NK clones that express 2DS1 mRNA and lack mRNA for 2DL1 demonstrates that activation by the C2 ligand and mAb cross-linking of 2DS1 in these clones induces IFN-γ. Furthermore, this C2 group-induced activation is inhibited by Abs to both HLA class I and the receptor. Collectively, these studies demonstrate that NK cells from 2DS1-positive donors are activated by target cells that express the C2 group as an alloantigen. This leads to increased IFN-γ-positive fresh NK cells and induces NK allocytotoxicity in IL2-propagated polyclonal NK cells and NK clones. This study also provides support for the concept that incompatibility for the HLA-KIR ligand groups C1, C2, and Bw4 dominates NK alloactivation in vitro. Copyright © 2007 by The American Association of Immunologists, Inc.
Keywords: controlled study; protein expression; transplantation, homologous; unclassified drug; human cell; nonhuman; animal cell; mouse; animal; animals; mice; interleukin 2; reverse transcription polymerase chain reaction; gene expression; cell line; cytotoxicity; monoclonal antibody; homozygosity; immunology; lymphocyte activation; gamma interferon; messenger rna; reverse transcriptase polymerase chain reaction; hla antigen class 2; hla antigen class 1; natural killer cell; killer cells, natural; killer cell immunoglobulin like receptor; target cell; cytotoxicity, immunologic; cell activation; alloantigen; hla antigen; hla antigens; allotransplantation; receptors, immunologic; alloimmunity; cross linking; immunoglobulin receptor; killer cell immunoglobulin like receptor 2ds1; kir receptors; kir2ds1 protein, human; b lymphoblast; lymphoblastoid cell
Journal Title: Journal of Immunology
Volume: 179
Issue: 2
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2007-07-15
Start Page: 854
End Page: 868
Language: English
PUBMED: 17617576
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 52" - "Export Date: 17 November 2011" - "CODEN: JOIMA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Charlotte Nini Gudme
    5 Gudme
  2. Katharine C Hsu
    149 Hsu
  3. Bo Dupont
    197 Dupont