Tumor recognition following Vgamma9Vdelta2 T cell receptor interactions with a surface F1-ATPase-related structure and apolipoprotein A-I.
Vgamma9Vdelta2 T lymphocytes, a major gammadelta T lymphocyte subset in humans, display cytolytic activity against various tumor cells upon recognition of yet uncharacterized structures. Here, we show that an entity related to the mitochondrial F1-ATPase is expressed on tumor cell surface and promotes tumor recognition by Vgamma9Vdelta2 T cells. When immobilized, purified F1-ATPase induces selective activation of this lymphocyte subset. The Vgamma9Vdelta2 T cell receptors (TCR) and the F1-ATPase also bind a delipidated form of apolipoprotein A-I (apo A-I), as demonstrated by surface plasmon resonance. Moreover, the presence of apo A-I in the culture medium is required for optimal activation of Vgamma9Vdelta2 T cells by tumors expressing F1-ATPase. This study thus describes an unanticipated tumor recognition mechanism by Vgamma9Vdelta2 lymphocytes and a possible link between gammadelta T cell immunity and lipid metabolism.
Scotet
Emmanuel
E
Inserm U601, Institut de Biologie, 9 quai Moncousu, F-44035 Nantes Cedex 01, France.
Martinez
Laurent O
LO
Grant
Ethan
E
Barbaras
Ronald
R
Jenö
Paul
P
Guiraud
Martine
M
Monsarrat
Bernard
B
Saulquin
Xavier
X
Maillet
Sophie
S
Estève
Jean-Pierre
JP
Lopez
Frédéric
F
Perret
Bertrand
B
Collet
Xavier
X
Bonneville
Marc
M
Champagne
Eric
E
D016632:Apolipoprotein A-I / Q000378:metabolism*; D006801:Humans; D007103:Immobilization; D019169:Jurkat Cells; D007700:Kinetics; D008024:Ligands; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology*; D011485:Protein Binding; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D013499:Surface Properties; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016632:Apolipoprotein A-I; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D006180:Proton-Translocating ATPases