HLA-E

Single nucleotide polymorphisms (SNPs) of HLA-E are related to the occurrence of many diseases, but their functions remain unclear. In this study, the function of SNPs at HLA-E rs76971248 and rs1264457 on the myeloid leukemia cells was analyzed by a progressive procedure, included genotyping, mRNA transcription, regulatory element, protein expression, and anti-tumor effect. The frequencies of rs76971248 G and rs1264457 G were found higher in myeloid leukemia patients than those in healthy blood donors (p < 0...

During pregnancy, the maternal immune system must allow and support the growth of the developing placenta while maintaining the integrity of the mother's body. The trophoblast's unique HLA signature is a key factor in this physiological process. This study focuses on decidual γδT cell populations and examines their expression of receptors that bind to non-classical HLA molecules, HLA-E and HLA-G. We demonstrate that decidual γδT cell subsets, including Vδ1, Vδ2, and double-negative (DN) Vδ1-/Vδ2- cells express HLA-specific regulatory receptors, such as NKG2C, NKG2A, ILT2, and KIR2DL4, each with varying dominance...

Preeclampsia is a syndrome with multiple etiologies. The diagnosis can be made without proteinuria in the presence of dysfunction of at least 1 organ associated with hypertension. The common pathophysiological pathway includes endothelial cell activation, intravascular inflammation, and syncytiotrophoblast stress. There is evidence to support, among others, immunologic causes of preeclampsia. Unlike defense immunology, reproductive immunology is not based on immunologic recognition systems of self/non-self and missing-self but on immunotolerance and maternal-fetal cellular interactions...

The commonly used antibodies 3D12 and 4D12 recognise the human leukocyte antigen E (HLA-E) protein. These antibodies bind distinct epitopes on HLA-E and differ in their ability to bind alleles of the major histocompatibility complex E (MHC-E) proteins of rhesus and cynomolgus macaques. We confirmed that neither antibody cross-reacts with classical HLA alleles, and used hybrids of different MHC-E alleles to map the regions that are critical for their binding. 3D12 recognises a region on the alpha 3 domain, with its specificity for HLA-E resulting from the amino acids present at three key positions (219, 223 and 224) that are unique to HLA-E, while 4D12 binds to the start of the alpha 2 domain, adjacent to the C terminus of the presented peptide...

PURPOSE: Early metastasis, in which immune escape plays a crucial role, is the leading cause of death in patients with uveal melanoma (UM); however, the molecular mechanism underlying UM immune escape remains unclear, which greatly limits the clinical application of immunotherapy for metastatic UM. METHODS: Transcriptome profiles were revealed by RNA-seq analysis. TALL-104 and NK-92MI-mediated cell killing assays were used to examine the immune resistance of UM cells...

NK cells play a decisive role in controlling hCMV infection by combining innate and adaptive-like immune reactions. The hCMV-derived VMAPRTLFL (LFL) peptide is a potent activator of NKG2C+ NK cells. Proposed here is an autologous system of LFL stimulation without T lymphocytes and exogenous cytokines that allows us to evaluate NK-cell hCMV-specific responses in more native settings. In this model, we evaluated LFL-induced IFNγ production, focusing on signaling pathways and the degranulation and proliferation of NK cells orchestrated by microenvironment cytokine production and analyzed the transcriptome of expanded NK cells...

OBJECTIVES: Immunotherapies targeting natural killer (NK) cell receptors have shown promise against leukaemia. Unfortunately, cancer immunosuppressive mechanisms that alter NK cell phenotype prevent such approaches from being successful. The study utilises advanced cytometry to examine how cancer immunosuppressive pathways affect NK cell phenotypic changes in clinical samples. METHODS: In this study, we conducted a high-dimensional examination of the cell surface expression of 16 NK cell receptors in paediatric patients with acute myeloid leukaemia and acute lymphoblastic leukaemia, as well as in samples of non-age matched adult peripheral blood (APB) and umbilical cord blood (UCB)...

Helicobacter pylori (H. pylori) seems to play causative roles in gastric cancers. H. pylori has also been detected in established gastric cancers. How the presence of H. pylori modulates immune response to the cancer is unclear. The cytotoxicity of natural killer (NK) cells, toward infected or malignant cells, is controlled by the repertoire of activating and inhibitory receptors expressed on their surface. Here, we studied H. pylori-induced changes in the expression of ligands, of activating and inhibitory receptors of NK cells, in the gastric adenocarcinoma AGS cells, and their impacts on NK cell responses...

Natural killer (NK) cells directly lysis the virus-infected cells through rapidly releasing cytotoxic mediators and cytokines. The balance between inhibitory and activated receptors on the surface of NK cells, as well as the corresponding ligands expressed on target cells are involved in the regulation of the cytotoxic function of NK cells. NKG2A is one of the highly anticipated inhibitory receptors expressed on NK cells, which can inhibit the cytotoxicity of NK cells to autologous normal tissue cells through interacting with the ligand HLA-E...

Recent strides in immunotherapy have illuminated the crucial role of CTLA-4 and PD-1/PD-L1 pathways in contemporary oncology, presenting both promises and challenges in response rates and adverse effects. This study employs a computational biology tool (in silico approach) to craft aptamers capable of binding to dual receptors, namely, inhibitory CTLA4 and NKG2A, thereby unleashing both T and NK cells and enhancing CD8+ T and NK cell functions for tumor cell lysis. Computational analysis highlighted AYA22T-R2-13 with HADDOCK scores of -78...

HLA-E molecules can present self- and pathogen-derived peptides to both natural killer (NK) cells and T cells. T cells that recognize HLA-E peptides via their T cell receptor (TCR) are termed donor-unrestricted T cells due to restricted allelic variation of HLA-E. The composition and repertoire of HLA-E TCRs is not known so far. We performed TCR sequencing on CD8+ T cells from 21 individuals recognizing HLA-E tetramers (TMs) folded with two Mtb -HLA-E-restricted peptides. We sorted HLA-E Mtb TM+ and TM- CD8+ T cells directly ex vivo and performed bulk RNA-sequencing and single-cell TCR sequencing...

Breast cancer (BC) is the second most common malignancy in the world. Numerous studies have demonstrated the association between human leukocyte antigen (HLA) and cancer. The occurrence and development of BC are closely linked to genetic factors. Human leukocyte antigens G and E (HLA-G and HLA-E) are non-classical major histocompatibility complex (MHC) class I molecules. These molecules play an important role in immune surveillance by inhibiting the cytotoxic and natural killer T cells responsible for immune escape...

BACKGROUND: Liver metastasis (Li) is one of the most common distant metastatic sites for gastric cancer. A deeper understanding of its mechanism of action from a bioinformatics perspective may provide new insights. Therefore, the aim of this study was to use single cell RNA sequencing (scRNA-seq) to evaluate cell subtypes and understand the molecular mechanism of gastric cancer Li. METHODS: The scRNA-seq data GSE163558 of gastric cancer and Li were downloaded from Gene Expression Omnibus (GEO)...

Natural killer (NK) cells are an appealing off-the-shelf, allogeneic cellular therapy due to their cytotoxic profile. However, their activity against solid tumors remains suboptimal in part due to the upregulation of NK-inhibitory ligands, such as HLA-E, within the tumor microenvironment. Here, we utilize CRISPR-Cas9 to disrupt the KLRC1 gene (encoding the HLA-E-binding NKG2A receptor) and perform non-viral insertion of a GD2-targeting chimeric antigen receptor (CAR) within NK cells isolated from human peripheral blood...

Previous investigators have used various anti-HLA-F monoclonal antibodies (mAbs) to demonstrate that the tissue distribution of HLA-F is highly restricted. Notably, these mAbs differed in their immunodiagnostic capabilities. Specifically, mAbs Fpep1.1 and FG1 detected HLA-F intracellularly in B cells but not on the cell surface, whereas mAb 3D11 detected HLA-F on the cell surface. The presence of HLA-F on T cells was recognized by mAb FG1 but not by mAb Fpep1.1. mAb 3D11 detected HLA-F on the cell surface of activated B cells and on peripheral blood lymphocytes, but not on the normal cells...

Allogeneic chimeric antigen receptor (CAR) T-cell therapies hold the potential to overcome many of the challenges associated with patient-derived (autologous) CAR T cells. Key considerations in the development of allogeneic CAR T-cell therapies include prevention of GvHD and suppression of allograft rejection. Here we describe preclinical data supporting the ongoing first-in-human clinical study, the CaMMouflage trial (NCT05722418), evaluating CB-011 in patients with relapsed/refractory multiple myeloma. CB-011 is a hypoimmunogenic, allogeneic anti-B cell maturation antigen (BCMA) CAR T-cell therapy candidate...

N6-methyladenosine (m6A) modification, as a common epigenetic modification, has been widely studied in autoimmune diseases. However, the role of m6A in the regulation of the immune microenvironment of ankylosing spondylitis (AS) remains unclear. Therefore, we aimed to investigate the effect of m6A modification on the immune microenvironment of AS. We first evaluated RNA modification patterns mediated by 26 m6A regulators in 52 AS samples and 20 healthy samples. Thereafter, an m6A related classifier composed of seven genes was constructed and could effectively distinguish healthy and AS samples...

In the immunological surveillance against cancer, natural killer (NK) cells are essential effectors that help eradicate altered cells. The complex interactions that occur between NK cells and the tumor microenvironment (TME) are thoroughly examined in this review. The review examines how cytokine stimulation affects NK cell activation, focusing on the dynamic modulation of NK cell function within the TME. It looks at NK cell-related biomarkers such as PD-1/PD-L1, methylation HOXA9 (Homeobox A9), Stroma AReactive Invasion Front Areas (SARIFA), and NKG2A/HLA-E, providing critical information about prognosis and treatment outcomes...

Human cytomegalovirus (HCMV)-specific adaptive NK cells are capable of recognizing viral peptides presented by HLA-E on infected cells via the NKG2C receptor. Using retroviral transduction, we have generated a K562-cell-based line expressing HLA-E in the presence of the HLA-E-stabilizing peptide, which has previously shown the capacity to enhance adaptive NK cell response. The obtained K562-21E cell line was employed to investigate proliferative responses of the CD57- NK cell subset of HCMV-seropositive and seronegative donors...

BACKGROUND: Immunotherapy is gaining momentum, but current treatments have limitations in terms of beneficiaries. Clear cell renal cell carcinoma (ccRCC) harbors the highest expression of human leukocyte antigen E (HLA-E), ligand of NKG2A, among all solid tumors. In this study, we aim to investigate the role of NKG2A+ CD8+ T cells in tumor microenvironment and its potential as a novel target in ccRCC. METHODS: This study included four independent cohorts, including 234 patients from Zhongshan cohort (ZSHC) who underwent partial or radical nephrectomy at Zhongshan Hospital, and 117 metastatic patients from metastatic Zhongshan cohort (ZSHC-metastatic renal cell carcinoma) who were treated with immune checkpoint inhibitor or tyrosine kinase inhibitor alone...