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Ecto-F1-ATPase and MHC Class I Close Association on cell membranes.

Abstract : Subunits of the mitochondrial ATP synthase complex are expressed on the surface of tumors, bind the TCR of human Vγ9/Vδ2 lymphocytes and promote their cytotoxicity. Present experiments show that detection of the complex (called ecto-F1-ATPase) at the cell surface by immunofluorescence correlates with low MHC-class I antigen expression. Strikingly, the α and β chains of ecto-F1-ATPase are detected in membrane protein precipitates from immunofluorescence-negative cells, suggesting that ATPase epitopes are masked. Removal of β2-microglobulin by mild acid treatment so that most surface MHC-I molecules become free heavy chains reveals F1-ATPase epitopes on MHC-I+ cell lines. Ecto- F1-ATPase is detected by immunofluorescence on primary fibroblasts which express moderate levels of MHC-I antigens. Upregulation of MHC-I on these cells following IFN-γ and/or TNF-α treatment induces a dose-dependent disappearance of F1-ATPase epitopes. Finally, biotinylated F1-ATPase cell surface components co-immunoprecipitate with MHC-I molecules confirming the association of both complexes on Raji cells. Confocal microscopy analysis of MHC-I and ecto-F1-ATPase β chain expression on HepG2 cells shows a colocalization of both complexes in punctate membrane domains. This demonstrates that the TCR target F1-ATPase is in close contact with MHC-I antigens which are known to control Vγ9/Vδ2 T cell activity through binding to natural killer inhibitory receptors.
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https://www.hal.inserm.fr/inserm-00150459
Contributor : Christine Peres <>
Submitted on : Thursday, March 6, 2008 - 1:55:54 PM
Last modification on : Tuesday, February 18, 2020 - 3:32:02 PM
Long-term archiving on: : Thursday, April 8, 2010 - 6:25:03 PM

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Pierre Vantourout, Laurent Martinez, Aurélie Fabre, Xavier Collet, Eric Champagne. Ecto-F1-ATPase and MHC Class I Close Association on cell membranes.. Molecular Immunology, Elsevier, 2008, 45 (2), pp.485-92. ⟨10.1016/j.molimm.2007.05.026⟩. ⟨inserm-00150459⟩

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