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Review
. 2025 Jul 16;14(14):1091.
doi: 10.3390/cells14141091.

Natural Killer (NK) Cell Alloreactivity in Haploidentical Stem Cell Transplantation

Mar Luis-Hidalgo  1 , José Luis Piñana  2 , Carlos Solano  2 , Dolores Planelles  1
Affiliations
Review

Natural Killer (NK) Cell Alloreactivity in Haploidentical Stem Cell Transplantation

Mar Luis-Hidalgo et al. Cells. .

Abstract

This paper conducts a literature review on the role of natural killer cells in haploidentical hematopoietic stem cell transplantation. Theoretical concepts related to KIR genes are introduced regarding their structure, nomenclature, genetic organization, polymorphism, and inheritance pattern, types of KIR proteins and receptors, HLA ligands for KIR receptors, and the definition of different NK alloreactivity prediction models for the donor of haploidentical hematopoietic stem cell transplantation and the recipient. These models include the following and consider incompatibility: ligand-ligand, receptor-ligand, gene-gene, and KIR haplotype models or the KIR-B donor group. These models consider the presence or absence of specific ligands or receptors and/or KIR genes in the donor and recipient to predict alloreactivity. Determining the best model for predicting KIR alloreactivity and its significance in donor selection algorithms for haploidentical transplantation is still under investigation.

Keywords: alloreactivity; haploidentical hematopoietic stem cell transplantation; natural killer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Missing-self theory. (A) NK cells avoid attacking healthy cells by detecting self HLA class I through inhibitory receptors. (B) However, they can damage allografts if HLA is missing (i), activating signals are strong (ii), or donor-specific antibodies trigger immune responses (iii). FcR, Fc receptor; i-KIR, inhibitory KIR; a-KIR, activating KIR; DSA, donor-specific antibodies. Source: Rajalingam, 2016 [11], under license (CC BY 4.0).
Figure 2
Figure 2
Structure of KIR proteins. Source: Pollock et al., 2022 [30], under license (CC BY-NC-ND 4.0).
Figure 3
Figure 3
Map of common KIR haplotypes in Caucasian populations. Each rectangle represents a KIR gene. Structural genes are shown in black (framework gene, Fw); and pseudogenes (Ps) are in white (2DP1) and gray (3DP1). Source: Traherne et al., 2016 [34], under license (CC BY 4.0).
Figure 4
Figure 4
Structure of inhibitory/activating KIRs and their class I HLA ligands. Source: Vollmers et al., 2021 [44], under license (CC BY 4.0).
Figure 5
Figure 5
Different alloreactivity NK cells models. Source: Chaisri and Leelayuwat, 2019 [66], under license (CC BY 3.0).
See this image and copyright information in PMC

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