Quantitative studies on biological water oxidation: a novel mechanism of T cells and antibodies.
Prior studies show that purified T cell receptors (TCRs) and antibodies catalyze the oxidation of water to H2O2 in the presence of singlet oxygen, but the comparative efficiencies of TCRs and antibodies in this process have not been reported. Since H2O2 has been shown to activate TCRs and selectively regulate redox sensitive TCR signaling pathways, it is important to understand the physiological significance of these recently uncovered processes. This new information might be used to develop new therapeutic tools for immune and inflammatory diseases. In this paper, we present data showing that under equivalent conditions Jurkat T cell membranes produce H2O2 at a rate of 457 pM/min/mg protein/muW/cm2 while IgG antibodies produce H2O2 at a rate of 192 pM/min/mg protein/muW/cm2. Taking into account the number of catalytic sites in a milligram of T cell membranes and IgGs, we calculate that TCRs catalyze H2O2 production at a specific rate that is about 10(6) times greater than the rate of IgGs. Based on these observations and calculations, we conclude that the comparatively high rate of H2O2 production by TCRs makes it more likely that this is a physiologically relevant process than the H2O2 production by IgGs. In addition, the catalytic rate for H2O2 production by TCRs is comparable to the rates of other physiologically important processes, such as catalysis by enzymes. This suggests that singlet oxygen-dependent, TCR mediated, H2O2 production is likely to be physiologically important, perhaps as H2O2 being a small molecule regulator of TCR signal transduction or a modulator of T cell gene transcription.
Trobaugh
Derek W
DW
Applied Biology and Biomedical Engineering, Rose-Hulman Institute of Technology, Terre Haute, IN 47803, USA.
Balcavage
Walter X
WX
Hughes
Ellen F
EF
Waite
Lee R
LR
Waite
Gabi Nindl
GN
D000906:Antibodies / Q000276:immunology / Q000378:metabolism*; D001834:Body Water / Q000378:metabolism*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism*; D003198:Computer Simulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000276:immunology / Q000378:metabolism*; D019169:Jurkat Cells; D008954:Models, Biological; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014867:Water / Q000378:metabolism*
D000906:Antibodies; D014867:Water; D006861:Hydrogen Peroxide