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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
Group 1 NKT cells recognize antigens presented in the context of the molecules CD1a, CD1b, and CD1c. CD1a is expressed at high levels in the skin epidermis and on Langerhans cells, CD1b on mDCs, and CD1c on B cells. CD1d is expressed by a broad variety of APC. The group 1 NKT cells therefore seem to act in cell-type/tissue-specific antigen recognition, perhaps as a means of providing tissue-specific immune responses. Many Group 1 CD1-restricted T cells are autoreactive, with IL-22-producing CD1a autoreactive T cells.
Personalized Immune Therapy
Published in II-Jin Kim, Cancer Genetics and Genomics for Personalized Medicine, 2017
Joost Hegmans, Lysanne Lievense, Joachim Aerts
Adoptive transfer of allogeneic, in vitro activated and expanded NK cells from haploidentical donors was proven potentially clinically effective in lung cancer [38]. NKT cells are currently exploited for cancer treatment by harnessing these cells with CD1d agonist ligands [39], or by adoptive transfer of NKT cells activated in vitro [40].
Phospholipid metabolites of the gut microbiota promote hypoxia-induced intestinal injury via CD1d-dependent γδ T cells
Published in Gut Microbes, 2022
Yuyu Li, Yuchong Wang, Fan Shi, Xujun Zhang, Yongting Zhang, Kefan Bi, Xuequn Chen, Lanjuan Li, Hongyan Diao
Specifically, γδ T cells can be recognized and activated by lipid antigens presented by CD1d, a nonpolymorphic major histocompatibility class (MHC) I-like molecule.19 CD1d molecules are mainly expressed on the surface of antigen-presenting cells, hepatocytes and intestinal epithelial cells.20–23 Sulfatide, a lipid antigen, in the blood can be presented to a specific subset of γδ T cells through CD1d on the surface of antigen-presenting cells.24 Exogenous lipid antigens such as phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) in the liver can also be presented to γδ T cells or natural killer T (NKT) cells through CD1d expressed by hepatocytes to promote activation.22,25–27 Moreover, γδ T cells in the mouse intestine can respond to lipid antigens presented by CD1d, including PE, PG and phosphatidylcholine (PC).23 Since the intestines constantly encounter lipid antigens derived from the commensal microbiota and acute hypoxia can significantly change the gut microbiota composition and structure, we speculate that lipid antigens derived from the intestinal microbiota may be related to the host immune response after acute hypoxia.
Epigenetic induction of CD1d expression primes lung cancer cells for killing by invariant natural killer T cells
Published in OncoImmunology, 2018
Éilis Dockry, Seónadh O'Leary, Laura E. Gleeson, Judith Lyons, Joseph Keane, Steven G. Gray, Derek G. Doherty
A mAb specific for CD1d was obtained from BD Biosciences (555749). MAbs specific for CD3 (300330), CD4 (344612), CD8α (300908), CD107a (328605) and the Vα24Jα18 TCR found on iNKT cells (clone 6B11; 342908) were obtained from BioLegend. Cells were stained with mAbs in PBS containing 1% bovine serum albumin and 0.02% sodium azide, and analysed using a FACSCanto II flow cytometer (BD Biosciences) and FlowJo software (Tree Star). Lymphocytes were gated on and any doublets or dead cells were excluded from the analysis. Single stained controls were used to set compensation parameters and fluorescence-minus-one controls were used to set gates. iNKT cell frequencies were expressed as percentages of lymphocytes. Absolute numbers of iNKT cells were determined from viable cell counts and expressed as cells/ml of blood or BAL.
Evolutionary Underpinnings of Innate-Like T Cell Interactions with Cancer
Published in Immunological Investigations, 2019
Maureen Banach, Jacques Robert
CD1d is the most characterized of CD1 genes. In contrast to classical MHC class Ia and nonclassical class Ib, CD1d presents a wide range of lipids or glycolipids as antigens to NKT cells (Adams and Luoma, 2013). Although microbial components were originally considered to be the major antigenic group, self- or neoplastic-derived antigens can also stimulate NKT cells (Porcelli and Modlin, 1999). Furthermore, self-antigens in the context of CD1d presentation are critical for NKT cell development and function (Godfrey et al., 2010). In combination with the non-polymorphic nature of CD1d, the lipid-derived antigens for NKT cell activation opens new and exciting avenues of research for therapeutic approaches (Godfrey et al., 2018; Moody and Suliman, 2017).