Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I. Academic Article uri icon

Overview

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.

publication date

  • August 2, 2016

Research

keywords

  • Autoantigens
  • Cord Blood Stem Cell Transplantation
  • HLA-B27 Antigen
  • Hematologic Neoplasms
  • Killer Cells, Natural
  • Receptors, KIR3DL1
  • Stromal Cells

Identity

PubMed Central ID

  • PMC5003427

Scopus Document Identifier

  • 84997831749

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2016.07.005

PubMed ID

  • 27496730

Additional Document Info

volume

  • 45

issue

  • 2