Lysosomal Lipases PLRP2 and LPLA2 Process Mycobacterial Multi-acylated Lipids and Generate T Cell Stimulatory Antigens
| Autor: | James A. Shayman, Lucia Mori, Diane Cala-De Paepe, Martine Gilleron, Emilie Layre, Gennaro De Libero, Frédéric Carrière, Naila Mebarek, Germain Puzo, Stéphane Canaan, Marco Lepore |
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| Přispěvatelé: | Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, University of Basel (Unibas), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), University of Michigan [Ann Arbor], University of Michigan System, Enzymologie interfaciale et de physiologie de la lipolyse (EIPL), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Endosome Acylation T-Lymphocytes T cell [SDV]Life Sciences [q-bio] Clinical Biochemistry Antigen presentation CD1 Biology Lymphocyte Activation Biochemistry Cell Line Mycobacterium law.invention 03 medical and health sciences Glycolipid Antigen law Drug Discovery medicine Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Antigens Molecular Biology ComputingMilieux_MISCELLANEOUS Pharmacology Antigen Presentation 030102 biochemistry & molecular biology Lipase Lipids Phospholipases A2 030104 developmental biology medicine.anatomical_structure Cell culture Recombinant DNA Molecular Medicine lipids (amino acids peptides and proteins) Lysosomes |
| Zdroj: | Cell Chemical Biology Cell Chemical Biology, Cell Press, 2016, 23 (9), pp.1147-1156. ⟨10.1016/j.chembiol.2016.07.021⟩ Cell Chemical Biology, Cell Press, 2016, pp.1147-1156. ⟨10.1016/j.chembiol.2016.07.021⟩ Cell Chemical Biology, 2016, 23 (9), pp.1147-1156. ⟨10.1016/j.chembiol.2016.07.021⟩ |
| ISSN: | 2451-9456 |
| DOI: | 10.1016/j.chembiol.2016.07.021⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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