Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I.
Document Type
Article
Publication Date
8-16-2016
JAX Source
Immunity 2016 Aug 16; 45(2):280-91.
Volume
45
Issue
2
First Page
280
Last Page
291
ISSN
1097-4180
PMID
27496730
Grant
CA23766, HL088134, CA08747, CA023766, CA034196
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. Immunity 2016 Aug 16; 45(2):280-91.
Recommended Citation
Boudreau J,
Liu X,
Zhao Z,
Zhang A,
Shultz LD,
Greiner D,
Dupont B,
Hsu K.
Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I. Immunity 2016 Aug 16; 45(2):280-91.