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Lipid Antigens: Revealing the Hidden Players in Adaptive Immune Responses.
Biomolecules
January 2025
Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 35147-99442, Iran.
Traditionally, research on the adaptive immune system has focused on protein antigens, but emerging evidence has underscored the essential role of lipid antigens in immune modulation. Lipid antigens are presented by CD1 molecules and activate invariant natural killer T (iNKT) cells and group 1 CD1-restricted T cells, whereby they impact immune responses to pathogens and tumors. Recent advances in mass spectrometry, imaging techniques, and lipidomics have revolutionized the identification and characterization of lipid antigens and enhanced our understanding of their structural diversity and functional significance.
View Article and Find Full Text PDFA double-edged sword role of IFN-γ-producing iNKT cells in sepsis: Persistent suppression of Treg cell formation in an Nr4a1-dependent manner.
iScience
December 2024
The Affiliated Zhongda Hospital, Clinical Medical College, Southeast University, Nanjing, Jiangsu, China.
Sepsis, a leading cause of mortality in intensive care units worldwide, lacks effective treatments for advanced-stage sepsis. Therefore, understanding the underlying mechanisms of this disease is crucial. This study reveals that invariant natural killer T (iNKT) cells have an opposing role in the progression of sepsis by suppressing regulatory T (Treg) cell differentiation and function.
View Article and Find Full Text PDFIdentification of α-galactosylceramide as an endogenous mammalian antigen for iNKT cells.
J Exp Med
February 2025
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Article Synopsis
- Invariant natural killer T (iNKT) cells are unique T cells that recognize lipid antigens through a molecule called CD1d, with α-galactosylceramide (α-GalCer) being the strongest known antigen.
- Researchers created a specialized system using supercritical fluid chromatography tandem mass spectrometry (SFC/MS/MS) to separate and identify different forms of hexosylceramide.
- Their findings revealed that α-GalCer, previously not found in mammals, is present in various biological fluids, representing the first identification of this potent antigen in mammalian systems.
Circulating immune landscape in melanoma patients undergoing anti-PD1 therapy reveals key immune features according to clinical response to treatment.
Front Immunol
December 2024
Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell Signaling & Cancer, Inserm U 1209, CNRS UMR, Université Grenoble Alpes, Grenoble, France.
Introduction: Immune checkpoint blockers (ICB) bring unprecedented clinical success, yet many patients endure immune mediated adverse effects and/or fail to respond. Predictive signatures of response to ICB and mechanisms of clinical efficacy or failure remain understudied. DC subsets, in network with conventional αβ T (T), NK, γδ T and iNKT cells, harbor pivotal roles in tumor control, yet their involvement in response to ICB remained underexplored.
View Article and Find Full Text PDFState of play in the molecular presentation and recognition of anti-tumor lipid-based analogues.
Front Immunol
December 2024
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
The Natural Killer T cells (NKT) are a unique subset of T lymphocytes that recognize lipid-based antigens that are presented by the monomorphic MHC-I-like molecule, CD1d. Over 30 years ago, the discovery of the glycolipid α-Galactosylceramide (α-GalCer) from the marine sponge , as a potent activator of the invariant Natural Killer T (iNKT) cells, has attracted great attention for its use in cancer immunotherapy. However, α-GalCer can initiate both pro-inflammatory T helper cell 1 (Th1) and anti-inflammatory Th2 type immune responses that can result in either enhanced or suppressed immunity in a somewhat unpredictable manner.
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