1. Lysosomal Lipases PLRP2 and LPLA2 Process Mycobacterial Multi-acylated Lipids and Generate T Cell Stimulatory Antigens.
- Author
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Gilleron M, Lepore M, Layre E, Cala-De Paepe D, Mebarek N, Shayman JA, Canaan S, Mori L, Carrière F, Puzo G, and De Libero G
- Subjects
- Acylation, Antigen Presentation genetics, Antigens metabolism, Cell Line, Humans, Lipase genetics, Lymphocyte Activation, Phospholipases A2 genetics, T-Lymphocytes cytology, Antigens immunology, Lipase metabolism, Lipids, Lysosomes enzymology, Mycobacterium metabolism, Phospholipases A2 metabolism, T-Lymphocytes immunology
- Abstract
Complex antigens require processing within antigen-presenting cells (APCs) to form T cell stimulatory complexes with CD1 antigen-presenting molecules. It remains unknown whether lipids with multi-acylated moieties also necessitate digestion by lipases to become capable of binding CD1 molecules and stimulate T cells. Here, we show that the mycobacterial tetra-acylated glycolipid antigens phosphatidyl-myo-inositol mannosides (PIM) are digested to di-acylated forms by pancreatic lipase-related protein 2 (PLRP2) and lysosomal phospholipase A2 (LPLA2) within APCs. Recombinant PLRP2 and LPLA2 removed the sn1- and sn2-bound fatty acids from the PIM glycerol moiety, as revealed by mass spectrometry and nuclear magnetic resonance studies. PLRP2 or LPLA2 gene silencing in APCs abolished PIM presentation to T cells, thus revealing an essential role of both lipases in vivo. These findings show that endosomal lipases participate in lipid antigen presentation by processing lipid antigens and have a role in T cell immunity against mycobacteria., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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