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

Marco Lepore, Claudia de Lalla, Ramanjaneyulu Gundimeda, Heiko Gsellinger, Michela Consonni, Claudio Garavaglia, Sebastiano Sansano, Francesco Piccolo, Andrea Scelfo, Daniel Häussinger, Daniela Montagna, Franco Locatelli, Chiara Bonini, Attilio Bondanza, Alessandra Forcina, Zhiyuan Li, Guanghui Ni, Fabio Ciceri, Paul Jenö, Chengfeng XiaLucia Mori, Paolo dellabona, Giulia Casorati, Gennaro de Libero

Research output: Contribution to journalArticle

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 selflipid 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.

Original languageEnglish
Pages (from-to)1363-1377
Number of pages15
JournalJournal of Experimental Medicine
Volume211
Issue number7
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Lepore, M., de Lalla, C., Gundimeda, R., Gsellinger, H., Consonni, M., Garavaglia, C., Sansano, S., Piccolo, F., Scelfo, A., Häussinger, D., Montagna, D., Locatelli, F., Bonini, C., Bondanza, A., Forcina, A., Li, Z., Ni, G., Ciceri, F., Jenö, P., ... de Libero, G. (2014). A novel self-lipid antigen targets human T cells against CD1c+ leukemias. Journal of Experimental Medicine, 211(7), 1363-1377. https://doi.org/10.1084/jem.20140410