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 immuno-deficient 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.
1.Univ Basel, Univ Hosp Basel, Dept Biomed, CH-4056 Basel, Switzerland 2.Univ Basel, Dept Chem, Nucl Magnet Resonance Lab, CH-4056 Basel, Switzerland 3.Univ Basel, Biozentrum, Dept Biochem, CH-4056 Basel, Switzerland 4.Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, Expt Immunol Unit, I-20132 Milan, Italy 5.Ist Sci San Raffaele, Expt Hematol Unit, I-20132 Milan, Italy 6.Ist Sci San Raffaele, Bone Marrow Transplantat Unit, I-20132 Milan, Italy 7.Univ Pavia, Dipartimento Pediat, Immunol Lab, I-27100 Pavia, Italy 8.Fdn IRCCS Policlin San Matteo, I-27100 Pavia, Italy 9.IRCCS Bambino Gesu Hosp, Dept Pediat Hematol Oncol, I-00165 Rome, Italy 10.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochemistry & Plant Resources We, Kunming 650201, Peoples R China 11.Singapore Immunol Network SIgN Agcy Sci Tech & Re, Singapore 138648, Singapore
Lepore,Marco;de Lalla,Claudia;Gundimeda,S. Ramanjaneyulu;Gsellinger,Heiko;Consonni,Michela;Garavaglia,Claudio;Sansano,Sebastiano;Piccolo,Francesco;Scelfo,Andrea;Haeussinger,Daniel;Montagna,Daniela;Locatelli,Franco;Bonini,Chiara;Bondanza,Attilio;Forcina,Alessandra;Li,Zhiyuan;Ni,Guanghui;Ciceri,Fabio;Jenoe,Paul;Xia,Chengfeng;Mori,Lucia;Dellabona,Paolo;Casorati,Giulia;De Libero,Gennaro.A novel self-lipid antigen targets human T cells against CD1c(+) leukemias,JOURNAL OF EXPERIMENTAL MEDICINE,2014,211(7):1360-1374