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: Marco Lepore, Claudia de Lalla, S 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 Xia, Lucia Mori, Paolo Dellabona, Giulia Casorati, Gennaro De Libero
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 211 Issue 7 Pg. 1363-77 (Jun 30 2014) ISSN: 1540-9538 [Electronic] United States
• PMID: 24935257 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Lepore et al.

Chemical References

• Antigens, CD1
• Autoantigens
• CD1C protein, human
• Glycoproteins
• Lysophospholipids
• lysophosphatidic acid

Topics

• Adolescent
• Animals
• Antigen Presentation (genetics, immunology)
• Antigens, CD1 (genetics, immunology)
• Autoantigens (genetics, immunology)
• Blast Crisis (genetics, immunology, pathology)
• Child
• Child, Preschool
• Female
• Gene Expression Regulation, Leukemic (genetics, immunology)
• Glycoproteins (genetics, immunology)
• Humans
• Immunologic Surveillance
• Jurkat Cells
• Leukemia, Myeloid, Acute (genetics, immunology, pathology)
• Lysophospholipids (genetics, immunology)
• Male
• Mice
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics, immunology, pathology)
• T-Lymphocytes (immunology, pathology)