TY - JOUR
T1 - HLA Class I Molecules as Immune Checkpoints for NK Cell Alloreactivity and Anti-Viral Immunity in Kidney Transplantation
AU - Duygu, Burcu
AU - Olieslagers, Timo I.
AU - Groeneweg, Mathijs
AU - Voorter, Christina E. M.
AU - Wieten, Lotte
N1 - Funding Information:
The authors wish to thank Diana van Bakel and Brigitte van der Linden – Krauth for their contribution to prepare the manuscript for submission. BioRender was used for preparation of the figures.
Publisher Copyright:
© Copyright © 2021 Duygu, Olieslagers, Groeneweg, Voorter and Wieten.
PY - 2021/7/6
Y1 - 2021/7/6
N2 - 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.
AB - 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.
KW - NK cell
KW - solid organ transplantation
KW - KIR
KW - NKG2A
KW - HLA class I
KW - NATURAL-KILLER-CELLS
KW - IMMUNOGLOBULIN-LIKE RECEPTOR
KW - LEUKOCYTE ANTIGEN-G
KW - 14-BP INSERTION/DELETION POLYMORPHISM
KW - HUMAN CYTOMEGALOVIRUS-INFECTION
KW - PARALLEL SEQUENCING PROCEDURES
KW - CODING REGION VARIABILITY
KW - DONOR-SPECIFIC ANTIBODIES
KW - 4 DISTINCT POPULATIONS
KW - IFN-ALPHA-BETA
U2 - 10.3389/fimmu.2021.680480
DO - 10.3389/fimmu.2021.680480
M3 - (Systematic) Review article
C2 - 34295330
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 680480
ER -