Non‐KIR NK cell receptors: Role in transplantation of allogeneic haematopoietic stem cells

Abstract

Natural killer (NK) cells are of major significance in patients after allogeneic haematopoietic stem cell transplantation (HSCT). They are the first subset of lymphocytes to appear in peripheral blood after transplantation and play an important role in the immune responses against cancer and viral infections. The function of NK cells is controlled by various surface receptors, of which type I integral proteins with immunoglobulin‐like domains (killer‐cell immunoglobulin‐like receptors, KIRs) have been the most extensively studied. The present review focuses on less studied NK cell receptors, such as type II integral proteins with lectin‐like domains (CD94/NKG2, NKG2D), natural cytotoxicity receptors (NCRs), immunoglobulin‐like transcripts (ILTs) and their ligands. Their potential role in patients with haematological disorders subjected to HSC transplant procedure in the context of post‐transplant complications such as viral reactivation and acute graft‐versus‐host disease (GvHD) will be presented and discussed.

Complex interactions of cellular players in chronic Graft-versus-Host Disease

“…Aside from KIRs, there is a wide variety of other NK cell receptors of both activating and inhibitory function. While not as polymorphic as KIRs, the genes coding for these receptors and their ligands harbor various important single nucleotide polymorphisms (SNPs) that can affect their function or expression ( 129 ), and may be associated with GVHD, including its chronic form ( 130 ). The natural cytotoxicity receptor (NCR) family includes three activating NK cell receptors: NKp46 (NCR1), NKp44 (NCR2), and NKp30 (NCR3) ( 131 – 133 ) with ligands that are not well defined ( 134 – 138 ).…”

Strategies to Optimise Oncolytic Viral Therapies: The Role of Natural Killer Cells

“…Less studied non-KIR NK cell receptors, including Natural Killer Group 2 (NKG2) receptors, natural cytotoxicity receptors (NCRs) and immunoglobulin-like transcripts (ILTs), are increasingly recognised to have potential roles in cancer immunotherapies. These are reviewed elsewhere [ 56 , 57 ]. Healthy cells express HLA class I molecules to generate inhibitory signals to avoid autoreactivity via inhibitory KIRs or other inhibitory NK receptors (e.g., NKG2A).…”

NKG2D Natural Killer Cell Receptor—A Short Description and Potential Clinical Applications

“…KIRs are a group of highly polymorphic molecules that recognize specific HLA-A, HLA-B and HLA-C allotypes (Table 1) [18]. Immunoglobulin-like transcripts (ILTs) constitute a group of NK cell receptors, members of which include inhibitory receptors ILT2, ILT3, and ILT4 [19]. As they can potentially suppress T cell responses and proliferation, they are thought to have a role in allograft tolerance during transplantation and cancer [20,21].…”

“…They are responsible for recognizing tumor cells and inducing cytotoxic effects. Studies suggest that they have an important role in a host response to hematopoietic stem cells transplant (HSCT) [19,22]. HLA-E KLRC1 12p13.2 [33,34] The CD94/NKG2 receptor family consist of seven distinct molecules with their genes being all located on chromosome 12 in humans [35].…”