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J Exp Med. 2014 Jun 30;211(7):1363-77. doi: 10.1084/jem.20140410. Epub 2014 Jun 16.

A novel self-lipid antigen targets human T cells against CD1c(+) leukemias.

Author information

1
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.
2
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.
3
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.
4
Laboratorio di Immunologia, Dipartimento di Pediatria, Università di Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
5
Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Hospital, 00165 Rome, Italy.
6
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
7
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.
8
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.

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.

PMID:
24935257
PMCID:
PMC4076585
DOI:
10.1084/jem.20140410
[Indexed for MEDLINE]
Free PMC Article

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