HLA Class I Molecules as Immune Checkpoints for NK Cell Alloreactivity and Anti-Viral Immunity in Kidney Transplantation

Burcu Duygu*, Timo I. Olieslagers, Mathijs Groeneweg, Christina E. M. Voorter, Lotte Wieten

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2 Citations (Web of Science)

Abstract

Natural killer (NK) cells are innate lymphocytes that can kill diseased- or virally-infected cells, mediate antibody dependent cytotoxicity and produce type I immune-associated cytokines upon activation. NK cells also contribute to the allo-immune response upon kidney transplantation either by promoting allograft rejection through lysis of cells of the transplanted organ or by promoting alloreactive T cells. In addition, they protect against viral infections upon transplantation which may be especially relevant in patients receiving high dose immune suppression. NK cell activation is tightly regulated through the integrated balance of signaling via inhibitory- and activating receptors. HLA class I molecules are critical regulators of NK cell activation through the interaction with inhibitory- as well as activating NK cell receptors, hence, HLA molecules act as critical immune checkpoints for NK cells. In the current review, we evaluate how NK cell alloreactivity and anti-viral immunity are regulated by NK cell receptors belonging to the KIR family and interacting with classical HLA class I molecules, or by NKG2A/C and LILRB1/KIR2DL4 engaging non-classical HLA-E or -G. In addition, we provide an overview of the methods to determine genetic variation in these receptors and their HLA ligands.

Original languageEnglish
Article number680480
Number of pages23
JournalFrontiers in Immunology
Volume12
DOIs
Publication statusPublished - 6 Jul 2021

Keywords

  • NK cell
  • solid organ transplantation
  • KIR
  • NKG2A
  • HLA class I
  • NATURAL-KILLER-CELLS
  • IMMUNOGLOBULIN-LIKE RECEPTOR
  • LEUKOCYTE ANTIGEN-G
  • 14-BP INSERTION/DELETION POLYMORPHISM
  • HUMAN CYTOMEGALOVIRUS-INFECTION
  • PARALLEL SEQUENCING PROCEDURES
  • CODING REGION VARIABILITY
  • DONOR-SPECIFIC ANTIBODIES
  • 4 DISTINCT POPULATIONS
  • IFN-ALPHA-BETA

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