NK cell tolerance of self-specific activating receptor KIR2DS1 in individuals with cognate HLA-C2 ligand Journal Article


Authors: Pittari, G.; Liu, X. R.; Selvakumar, A.; Zhao, Z.; Merino, E. ; Huse, M.; Chewning, J. H.; Hsu, K. C.; Dupont, B.
Article Title: NK cell tolerance of self-specific activating receptor KIR2DS1 in individuals with cognate HLA-C2 ligand
Abstract: NK cells are regulated by inhibiting and activating cell surface receptors. Most inhibitory receptors recognize MHC class I Ags and protect healthy cells from NK cell-mediated autoaggression. However, certain activating receptors, including the human activating killer cell Ig-like receptor (KIR) 2DS1, also recognize MHC class I. This fact raises the question of how NK cells expressing such activating receptors are tolerized to host tissues. We investigated whether the presence of HLA-C2, the cognate ligand for 2DS1, induces tolerance in 2DS1-expressing NK cells. Anti-HLA-C2 activity could be detected in vitro in some 2DS1 positive NK clones irrespective of the presence or absence of HLA-C2 ligand in the donor. The frequency of anti-HLA-C2 reactivity was high in donors homozygous for HLA-C1. Surprisingly, no significant difference was seen in the frequency of anti-HLA-C2 cytotoxicity in donors heterozygous for HLA-C2 and donors without HLA-C2 ligand. However, donors homozygous for HLA-C2, compared with all other donors, had significantly reduced frequency of anti-HLA-C2 reactive clones. The 2DS1 positive clones that express inhibitory KIR for self-HLA class I were commonly noncytotoxic, and anti-HLA-C2 cytotoxicity was nearly exclusively restricted to 2DS1 single positive clones lacking inhibitory KIR. 2DS1 single positive NK clones with anti-HLA-C2 reactivity were also present posttransplantation in HLA-C2 positive recipients of hematopoietic stem cell transplants from 2DS1 positive donors. These results demonstrate that many NK cells with anti-HLA-C2 reactivity are present in HLA-C1 homozygous and heterozygous donors with 2DS1. In contrast, 2DS1 positive clones from HLA-C2 homozygous donors are frequently tolerant to HLA-C2. Copyright © 2013 by The American Association of Immunologists, Inc.
Journal Title: Journal of Immunology
Volume: 190
Issue: 9
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2013-05-01
Start Page: 4650
End Page: 4660
Language: English
DOI: 10.4049/jimmunol.1202120
PROVIDER: scopus
PMCID: PMC3643210
PUBMED: 23554313
DOI/URL:
Notes: --- - "Export Date: 3 June 2013" - "CODEN: JOIMA" - "Source: Scopus"
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MSK Authors
  1. Katharine C Hsu
    148 Hsu
  2. Morgan Huse
    45 Huse
  3. Xiao-Rong Liu
    21 Liu
  4. Zeguo Zhao
    14 Zhao
  5. Bo Dupont
    196 Dupont