Cell-extrinsic MHC class I molecule engagement augments human NK cell education programmed by cell-intrinsic MHC class I Journal Article


Authors: Boudreau, J. E.; Liu, X. R.; Zhao, Z.; Zhang, A.; Shultz, L. D.; Greiner, D. L.; Dupont, B.; Hsu, K. C.
Article Title: Cell-extrinsic MHC class I molecule engagement augments human NK cell education programmed by cell-intrinsic MHC class I
Abstract: The effector potential of NK cells is counterbalanced by their sensitivity to inhibition by “self” MHC class I molecules in a process called “education.” In humans, interactions between inhibitory killer immunoglobulin-like receptors (KIR) and human MHC (HLA) mediate NK cell education. In HLA-B∗27:05+ transgenic mice and in patients undergoing HLA-mismatched hematopoietic cell transplantation (HCT), NK cells derived from human CD34+ stem cells were educated by HLA from both donor hematopoietic cells and host stromal cells. Furthermore, mature human KIR3DL1+ NK cells gained reactivity after adoptive transfer to HLA-B∗27:05+ mice or bone marrow chimeric mice where HLA-B∗27:05 was restricted to either the hematopoietic or stromal compartment. Silencing of HLA in primary NK cells diminished NK cell reactivity, while acquisition of HLA from neighboring cells increased NK cell reactivity. Altogether, these findings reveal roles for cell-extrinsic HLA in driving NK cell reactivity upward, and cell-intrinsic HLA in maintaining NK cell education. © 2016 Elsevier Inc.
Journal Title: Immunity
Volume: 45
Issue: 2
ISSN: 1074-7613
Publisher: Cell Press  
Date Published: 2016-08-16
Start Page: 280
End Page: 291
Language: English
DOI: 10.1016/j.immuni.2016.07.005
PROVIDER: scopus
PMCID: PMC5003427
PUBMED: 27496730
DOI/URL:
Notes: Article -- Export Date: 3 January 2017 -- Source: Scopus
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MSK Authors
  1. Katharine C Hsu
    148 Hsu
  2. Xiao-Rong Liu
    21 Liu
  3. Zeguo Zhao
    14 Zhao
  4. Bo Dupont
    196 Dupont
  5. Aaron   Zhang
    2 Zhang