title: A novel self-lipid antigen targets human T cells against CD1c(+) leukemias.
abstract: T cells that recognize self-lipids presented by CD1c are frequent in the peripheral blood of healthy individuals and kill transformed hematopoietic cells, but little is known about their antigen specificity and potential antileukemia effects. We report that CD1c self-reactive T cells recognize a novel class of self-lipids, identified as methyl-lysophosphatidic acids (mLPAs), which are accumulated in leukemia cells. Primary acute myeloid and B cell acute leukemia blasts express CD1 molecules. mLPA-specific T cells efficiently kill CD1c(+) acute leukemia cells, poorly recognize nontransformed CD1c-expressing cells, and protect immunodeficient mice against CD1c(+) human leukemia cells. The identification of immunogenic self-lipid antigens accumulated in leukemia cells and the observed leukemia control by lipid-specific T cells in vivo provide a new conceptual framework for leukemia immune surveillance and possible immunotherapy.
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel; Nuclear Magnetic Resonance Laboratory, Department of Chemistry; and Department of Biochemistry, Biozentrum; University of Basel, 4056 Basel, Switzerland Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lepore
authors.affiliation: Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: de Lalla
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel; Nuclear Magnetic Resonance Laboratory, Department of Chemistry; and Department of Biochemistry, Biozentrum; University of Basel, 4056 Basel, Switzerland.
authors.forename: S Ramanjaneyulu
authors.initials: SR
authors.lastname: Gundimeda
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel; Nuclear Magnetic Resonance Laboratory, Department of Chemistry; and Department of Biochemistry, Biozentrum; University of Basel, 4056 Basel, Switzerland.
authors.forename: Heiko
authors.initials: H
authors.lastname: Gsellinger
authors.affiliation: Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Consonni
authors.affiliation: Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Garavaglia
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel; Nuclear Magnetic Resonance Laboratory, Department of Chemistry; and Department of Biochemistry, Biozentrum; University of Basel, 4056 Basel, Switzerland.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Sansano
authors.affiliation: Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piccolo
authors.affiliation: Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scelfo
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel; Nuclear Magnetic Resonance Laboratory, Department of Chemistry; and Department of Biochemistry, Biozentrum; University of Basel, 4056 Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Häussinger
authors.affiliation: Laboratorio di Immunologia, Dipartimento di Pediatria, Università di Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Montagna
authors.affiliation: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Hospital, 00165 Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bonini
authors.affiliation: Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Attilio
authors.initials: A
authors.lastname: Bondanza
authors.affiliation: Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Forcina
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ni
authors.affiliation: Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel; Nuclear Magnetic Resonance Laboratory, Department of Chemistry; and Department of Biochemistry, Biozentrum; University of Basel, 4056 Basel, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Jenö
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Xia
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel; Nuclear Magnetic Resonance Laboratory, Department of Chemistry; and Department of Biochemistry, Biozentrum; University of Basel, 4056 Basel, Switzerland Singapore Immunology Network (SIgN), Agency for Science, Technology, and Research, Singapore 138648 gennaro.delibero@unibas.ch casorati.giulia@hsr.it dellabona.paolo@hsr.it lucia_mori@immunol.a-star.edu.sg.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mori
authors.affiliation: Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy gennaro.delibero@unibas.ch casorati.giulia@hsr.it dellabona.paolo@hsr.it lucia_mori@immunol.a-star.edu.sg.
authors.forename: Paolo
authors.initials: P
authors.lastname: Dellabona
authors.affiliation: Experimental Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy gennaro.delibero@unibas.ch casorati.giulia@hsr.it dellabona.paolo@hsr.it lucia_mori@immunol.a-star.edu.sg.
authors.forename: Giulia
authors.initials: G
authors.lastname: Casorati
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel; Nuclear Magnetic Resonance Laboratory, Department of Chemistry; and Department of Biochemistry, Biozentrum; University of Basel, 4056 Basel, Switzerland Singapore Immunology Network (SIgN), Agency for Science, Technology, and Research, Singapore 138648 gennaro.delibero@unibas.ch casorati.giulia@hsr.it dellabona.paolo@hsr.it lucia_mori@immunol.a-star.edu.sg.
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
mesh_terms: D000293:Adolescent; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D001752:Blast Crisis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007157:Immunologic Surveillance; D019169:Jurkat Cells; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008246:Lysophospholipids / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D018949:Antigens, CD1; D001324:Autoantigens; C437944:CD1C protein, human; D006023:Glycoproteins; D008246:Lysophospholipids; C032881:lysophosphatidic acid