Lysosomal Lipases PLRP2 and LPLA2 Process Mycobacterial Multi-acylated Lipids and Generate T Cell Stimulatory Antigens.
- Gilleron M Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse 31077, France. Electronic address: martine.gilleron@ipbs.fr.
- Lepore M Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
- Layre E Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse 31077, France.
- Cala-De Paepe D Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse 31077, France.
- Mebarek N Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse 31077, France.
- Shayman JA Nephrology Division, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
- Canaan S CNRS, Aix Marseille Université, UMR7282 Enzymology at Interfaces and Physiology of Lipolysis, Marseille Cedex 20 13402, France.
- Mori L Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
- Carrière F CNRS, Aix Marseille Université, UMR7282 Enzymology at Interfaces and Physiology of Lipolysis, Marseille Cedex 20 13402, France.
- Puzo G Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse 31077, France.
- De Libero G Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore. Electronic address: gennaro.delibero@unibas.ch.
- 2016-09-24
Published in:
- Cell chemical biology. - 2016
Acylation
Antigen Presentation
Antigens
Cell Line
Humans
Lipase
Lipids
Lymphocyte Activation
Lysosomes
Mycobacterium
Phospholipases A2
T-Lymphocytes
English
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1016/j.chembiol.2016.07.021
- PMID 27662254
- Persistent URL
- https://sonar.ch/global/documents/159945
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