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

Fingerprint

Autoantigens
Leukemia
T-Lymphocytes
Lipids
Lysophospholipids
B-Cell Leukemia
Antigens
Myeloid Cells
Immunotherapy
Self Report

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Lepore, M., de Lalla, C., Gundimeda, R., Gsellinger, H., Consonni, M., Garavaglia, C., ... 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

A novel self-lipid antigen targets human T cells against CD1c+ leukemias. / Lepore, Marco; de Lalla, Claudia; Gundimeda, Ramanjaneyulu; Gsellinger, Heiko; Consonni, Michela; Garavaglia, Claudio; Sansano, Sebastiano; Piccolo, Francesco; Scelfo, Andrea; Häussinger, Daniel; Montagna, Daniela; Locatelli, Franco; Bonini, Chiara; Bondanza, Attilio; Forcina, Alessandra; Li, Zhiyuan; Ni, Guanghui; Ciceri, Fabio; Jenö, Paul; Xia, Chengfeng; Mori, Lucia; dellabona, Paolo; Casorati, Giulia; de Libero, Gennaro.

In: Journal of Experimental Medicine, Vol. 211, No. 7, 2014, p. 1363-1377.

Research output: Contribution to journalArticle

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, Xia, C, Mori, L, dellabona, P, Casorati, G & de Libero, G 2014, 'A novel self-lipid antigen targets human T cells against CD1c+ leukemias', Journal of Experimental Medicine, vol. 211, no. 7, pp. 1363-1377. https://doi.org/10.1084/jem.20140410
Lepore, Marco ; de Lalla, Claudia ; Gundimeda, Ramanjaneyulu ; Gsellinger, Heiko ; Consonni, Michela ; Garavaglia, Claudio ; Sansano, Sebastiano ; Piccolo, Francesco ; Scelfo, Andrea ; Häussinger, Daniel ; Montagna, Daniela ; Locatelli, Franco ; Bonini, Chiara ; Bondanza, Attilio ; Forcina, Alessandra ; Li, Zhiyuan ; Ni, Guanghui ; Ciceri, Fabio ; Jenö, Paul ; Xia, Chengfeng ; Mori, Lucia ; dellabona, Paolo ; Casorati, Giulia ; de Libero, Gennaro. / A novel self-lipid antigen targets human T cells against CD1c+ leukemias. In: Journal of Experimental Medicine. 2014 ; Vol. 211, No. 7. pp. 1363-1377.
@article{e25bae2ad2d4439297df3bca77e9dd19,
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 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.",
author = "Marco Lepore and {de Lalla}, Claudia and Ramanjaneyulu Gundimeda and Heiko Gsellinger and Michela Consonni and Claudio Garavaglia and Sebastiano Sansano and Francesco Piccolo and Andrea Scelfo and Daniel H{\"a}ussinger and Daniela Montagna and Franco Locatelli and Chiara Bonini and Attilio Bondanza and Alessandra Forcina and Zhiyuan Li and Guanghui Ni and Fabio Ciceri and Paul Jen{\"o} and Chengfeng Xia and Lucia Mori and Paolo dellabona and Giulia Casorati and {de Libero}, Gennaro",
year = "2014",
doi = "10.1084/jem.20140410",
language = "English",
volume = "211",
pages = "1363--1377",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "7",

}

TY - JOUR

T1 - A novel self-lipid antigen targets human T cells against CD1c+ leukemias

AU - Lepore, Marco

AU - de Lalla, Claudia

AU - Gundimeda, Ramanjaneyulu

AU - Gsellinger, Heiko

AU - Consonni, Michela

AU - Garavaglia, Claudio

AU - Sansano, Sebastiano

AU - Piccolo, Francesco

AU - Scelfo, Andrea

AU - Häussinger, Daniel

AU - Montagna, Daniela

AU - Locatelli, Franco

AU - Bonini, Chiara

AU - Bondanza, Attilio

AU - Forcina, Alessandra

AU - Li, Zhiyuan

AU - Ni, Guanghui

AU - Ciceri, Fabio

AU - Jenö, Paul

AU - Xia, Chengfeng

AU - Mori, Lucia

AU - dellabona, Paolo

AU - Casorati, Giulia

AU - de Libero, Gennaro

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84903754024&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903754024&partnerID=8YFLogxK

U2 - 10.1084/jem.20140410

DO - 10.1084/jem.20140410

M3 - Article

C2 - 24935257

AN - SCOPUS:84903754024

VL - 211

SP - 1363

EP - 1377

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 7

ER -