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The maternal immune system during pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Innate effector cells include NK cells, which are of lymphocytic lineage. In contrast to other lymphocytes, NK cells do not possess the CD3 complex or clonally expand in response to antigen stimulation. NK cells do possess many activating and inhibitory receptors of two major structural classes, those of the immunoglobulin superfamily [killer immunoglobulin-like receptors (KIRs) and LIRs] and of the C-type lectin-like family (Ly49, NKG2D, and CD94/NKG2) (39). These receptors recognize cell surface molecules, such as major histocompatibility complex (MHC)-1 glycoproteins and their structural relatives. The balance between activating and inhibiting signals determines the behavior of the NK cell. If the balance favors activation, the NK cell kills the target cell in much the same way as a cytotoxic T-lymphocyte, by forming an immunologic synapse, perforating the target cell membrane, and infusing granzyme into the cell, which initiates apoptosis of the target cell.
T lymphocyte populations within the lamina propria
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Thomas T. MacDonald, Antonio Di Sabatino
As the name says, natural killer T (NKT) cells share phenotypic and functional features with both conventional NK cells and T cells, such as the expression of NK1.1/CD161, Ly49 and NKG2, CD3 and an αβ TCR. NKT cells are characterized by a relatively limited TCR usage. Type I NKT cells in mice express the evolutionarily conserved invariant TCRα chain Vα14-Jα18 associated with a limited set of β chains, Vβ8.2, Vβ7, and Vβ2 segments. Human type I NKT cells express the invariant TCRα chain Vα24-Jα18 paired with Vβ11. Type II (nonclassical) NKT cells in mice and man tend to use diverse α and β chains. Type I NKT cells can be double negative or CD4+ in mice, and in humans, can be CD4+, CD8+, or double negative. All murine and human type I NKT cells but not type II cells bind the glycolipid α-galactosylceramide, NKT cells recognize glycolipids via the MHC-I like molecules CD1. In humans there are five CDI molecules (CD1a–e) with CD1d the best investigated. Mice only express CD1d.
Monocyte and lymphocyte membrane markers: Ontogeny and clinical significance
Published in Gabriel Virella, Medical Immunology, 2019
Scott Sugden, Damien Montamat-Sicotte, Karen K. Yam, Joseph Murphy, Bader Yassine Diab, Virginia Litwin
Historically, NK cells were defined as mediators of MHC non-restricted cytolysis because of their ability to lyse allogeneic as well as autologous virally infected or transformed targets. However, the observation that NK cells preferentially lyse target cells that expressed low levels or no MHC class I antigens precipitated the study of MHC class I receptors on NK cells. Two distinct MHC class I receptor families have been described in humans: the KIRs and CD94/NKG2A, each of which rely on ITIM sequences in the cytoplasmic domains to mediate inhibitory signaling. NK cell proliferation, cytotoxicity, and cytokine production are downregulated as a consequence of MHC class I–NK receptor interaction. KIR family members recognize classical MHC class I and are expressed on overlapping subsets of human NK cells, γδTCR+ T cells, and memory/effector αβTCR+ T cells. There are 15 genes in the KIR family coding for type I transmembrane glycoproteins containing two or three Ig-like domains. Variability also exists within the cytoplasmic domains. The KIRs family members with the longer cytoplasmic tails contains one to two ITIM sequences. The KIRs with the shorter cytoplasmic region do not contain ITIM and form a transmembrane association with ITAMs bearing the DAP12adapter protein, delivering activation rather than inhibitory signals.CD94 and NKG2 are type II membrane proteins of the C-type lectin-like family, which form disulfide-linked heterodimers. They recognize the nonclassical MHC molecule HLA-E. CD94 associates with human NKG2 proteins (NKG2A or NKG2C) and is expressed on most NK cells, γδTCR+ T cells, and a subset memory/effector CD8+αβTCR+ T cells. CD94-NKG2A contains an ITIM in its cytoplasmic domain and functions as an inhibitory receptor, whereas CD94-NKG2C functions as an activation receptor when associated with DAP-12. IL-15, Il-2, and TGF-β induce CD94-NKG2 expression.
Dissecting the cellular components of ex vivo γδ T cell expansions to optimize selection of potent cell therapy donors for neuroblastoma immunotherapy trials
Published in OncoImmunology, 2022
Hunter C. Jonus, Rebecca E. Burnham, Andrew Ho, Adeiye A. Pilgrim, Jenny Shim, Christopher B. Doering, H. Trent Spencer, Kelly C. Goldsmith
Both expanded γδ T cells and NK cells expressed uniformly high levels (>90% positive) of activating receptors that may promote tumor recognition, including CD314 (NKG2D) and CD226 (DNAM-1) (Figure 3c). Although both were identified post-expansion, γδ T cells and NK cells expressed lower levels of inhibitory receptors and exhaustion markers compared to activating receptors (Figure 3d and 3e). Of note, CD159a (NKG2A), a classical inhibitory member of the NKG2 family, was identified on both expanded γδ T cells and NK cells (Figure 3d). CD279 (PD-1), CD366 (TIM3) and TIGIT were the most highly expressed exhaustion markers identified post-expansion; increased levels of TIGIT were observed on the expanded NK cell population compared to expanded γδ T cells (Figure 3e). Additionally, both expanded γδ T cells and NK cells expressed CD95 (Fas), with γδ T cells at a higher frequency than NK cells, and lower CD178 (FasL), both markers involved in apoptotic signaling. (Figure 3f).
Increased Peripheral NKG2A-NKG2D+CD3-CD16+CD56dim NK Cell Subset Was Positively Correlated with Antiphospholipid Antibodies in Patients of Obstetric Antiphospholipid Syndrome
Published in Immunological Investigations, 2022
Yinmei Zhang, Yang Zhao, Wenzhe Si, Boxin Yang, Mingmei Lin, Jiajia Zheng, Liyan Cui
NK cells express a series of receptors to identify relevant ligands on target cells, which can activate their cytotoxic and secretory functions (Tabiasco et al. 2006). The NKG2 family belongs to the c-type lectin family, which include inhibitory receptors NKG2A, NKG2B, and activating receptors NKG2C, NKG2D and NKG2E (Ryan et al. 2001). NKG2 family receptors can directly activate or inhibit peripheral NK cells, and are considered as the main activated receptors mediating NK cell cytotoxic function (Kumar 2018). Natural cytotoxicity receptors (NCR) belong to another important NK receptor families, which consist of three activating receptors NKp46, NKp44 and NKp30. Therefore, whether activating and inhibiting receptor phenotypes change in OAPS patients need to be further explored (Tabiasco et al. 2006).
Association between rs1049174 NKG2D gene polymorphism and idiopathic recurrent spontaneous abortion in Iranian women: a case-control study
Published in Journal of Obstetrics and Gynaecology, 2021
Amir Abdian Asl, Fereshteh Vaziri Nezamdoust, Farzaneh Fesahat, Akram Astani, Meisam Barati, Pourya Raee, Abolghasem Asadi-Saghandi
NKG2D is encoded by the killer cell lectin-like receptor subfamily K member 1 (KLRK1) gene located on human chromosome 12p within the natural killer group 2 (NKG2) complex (Glienke et al. 1998). A single nucleotide polymorphism (SNP: rs1049174) in the 3′-untranslated regions (3'UTR) of the NKG2D gene is associated with high and low NK activity (HNK and LNK, respectively). Some studies have shown that the G allele of NKG2D rs1049174 may contribute to HNK phenotype; whereas, the C allele results in low NK activity phenotype (Hayashi et al. 2006; Furue, Kumimoto, et al. 2008; Furue, Matsuo, et al. 2008). Several studies have been conducted to explore the role of NKG2D and its ligand expression in pregnancy outcome (Mincheva-Nilsson et al. 2006; Hedlund et al. 2009; Marlin et al. 2012; Mei et al. 2012; Hizem et al. 2014; Yougbare et al. 2015). On the other hand, numerous studies have investigated the association between NKG2D gene polymorphism and cancer susceptibility (Espinoza et al. 2016; Gimeno et al. 2019), viral infections (Asadi-Saghandi et al. 2016; Zingoni et al. 2018), and autoimmune diseases (Mariaselvam et al. 2017). Given that few studies have investigated the association between NKG2D gene polymorphism and RSA risk, the current study was carried out to explore the correlation between NKG2D polymorphism (rs1049174 G/C) and RSA risk in Iranian women.