Research Article

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

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Science  16 Apr 2015:
DOI: 10.1126/science.aaa7516

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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 CTL.

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