Oxidative stress impairs intracellular events involved in antigen processing and presentation to T cells.
For T cells to recognize foreign antigens, the latter must be processed into peptides and associated to major histocompatibility complex (MHC) class II molecules by antigen-presenting cells (APC). APCs frequently operate under stress conditions induced by tissue damage, antigens, or inflammatory reactions. We analyze the effects of oxidative stress on intracellular processing using APC B cell lines. Before being tested for APC function, B cells (IIA1.6) were exposed for 2 hours to hydrogen peroxide (H2O2), a treatment that impairs their capacity to stimulate specific T cell clones. Because paraformaldehyde-fixed H2O2-treated B cells can still present extracellular peptides to T cell clones, the intracellular events of processing were investigated. Purified lysosomes from H2O2-treated B cells show increased proteolytic activity and increased generation of antigenic peptides. In addition, H2O2 treatment targets antigens to compartments that express low levels of MHC II and proteins (H-2M, H-2O) required for peptide loading onto this molecule. Finally, we suggest that impairment of antigen processing by oxidative stress reduces the induction of a T cell's response because H2O2 decreases the activation of naive T lymphocytes by dendritic cells. Together, these data indicate that oxidative stress inhibits the capacity of APCs to process antigens and to initiate a primary T cell response. The role of such modifications on the outcome of the specific immune response is discussed.
Preynat-Seauve
Olivier
O
Laboratoire d'immunochimie, INSERM U548, ICH/DRDC/CEA-Grenoble, Université Joseph Fourier, 38054 Grenoble Cedex 09, France.
Coudurier
Sylvia
S
Favier
Alain
A
Marche
Patrice-Noël
PN
Villiers
Christian
C
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D011992:Endosomes / Q000187:drug effects; D006825:Hybridomas / Q000187:drug effects / Q000276:immunology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects; D051379:Mice; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D010455:Peptides / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*
D016877:Oxidants; D010455:Peptides; D006861:Hydrogen Peroxide