The protein LEM promotes CD8⁺ T cell immunity through effects on mitochondrial respiration

Protective CD8⁺ T cell–mediated immunity requires a massive expansion in cell number and the development of long-lived memory cells. Using forward genetics in mice, we identified an orphan protein named lymphocyte expansion molecule (LEM) that promoted antigen-dependent CD8⁺ T cell proliferation, ef...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2015-05, Vol.348 (6238), p.995-1001
Main Authors: Okoye, Isobel, Wang, Lihui, Pallmer, Katharina, Richter, Kirsten, Ichimura, Takahuru, Haas, Robert, Crouse, Josh, Choi, Onjee, Heathcote, Dean, Lovo, Elena, Mauro, Claudio, Abdi, Reza, Oxenius, Annette, Rutschmann, Sophie, Ashton-Rickardt, Philip G.
Format: Article
Language:English
Subjects:
Construction
Cytotoxicity
Genes
Genetics
Immunity
Immunology
Memory (computers)
Mice
Mitochondria
Protective
Proteins
T cell receptors
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Summary:Protective CD8⁺ T cell–mediated immunity requires a massive expansion in cell number and the development of long-lived memory cells. Using forward genetics in mice, we identified an orphan protein named lymphocyte expansion molecule (LEM) that promoted antigen-dependent CD8⁺ T cell proliferation, effector function, and memory cell generation in response to infection with lymphocytic choriomeningitis virus. Generation of LEM-deficient mice confirmed these results. Through interaction with CR6 interacting factor (CRIF1), LEM controlled the levels of oxidative phosphorylation (OXPHOS) complexes and respiration, resulting in the production of pro-proliferative mitochondrial reactive oxygen species (mROS). LEM provides a link between immune activation and the expansion of protective CD8⁺ T cells driven by OXPHOS and represents a pathway for the restoration of long-term protective immunity based on metabolically modified cytotoxic CD8⁺ T cells.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aaa7516