Cognate MHC-TCR interaction leads to apoptosis of antigen-presenting cells.
Antigen presentation to T lymphocytes has been characterized extensively in terms of T lymphocyte activation and eventual cell death. In contrast, little is known about the consequences of antigen presentation for the antigen-presenting cell (APC). We have determined the outcome of major histocompatibility complex class II-restricted peptide presentation to a specific T cell. We demonstrate that specific T lymphocyte interaction with peptide-presenting APCs led to apoptosis in the APC population. In contrast, T lymphocyte interaction with nonpeptide-loaded APCs or APCs loaded with monosubstituted peptide failed to induce T lymphocyte secretion of interleukin-2 and APC apoptosis. Phosphatidylserine externalization and mitochondrial depolarization were used to evaluate APC apoptosis. Fas/Fas ligand interactions were not required, but cytoskeletal integrity and caspase activation were essential for APC apoptosis. Antigen presentation leading to T lymphocyte activation is therefore coordinated with apoptosis in the APC population and could provide a mechanism of immune response regulation by eliminating APCs, which have fulfilled their role as specific ligands for T lymphocyte activation. This pathway may have particular importance for APCs, which are not sensitive to death receptor-induced apoptosis.
INSERM U396, Institut des Cordeliers, 75006 Paris, France.
Niclas
N
Setterblad
Vincent
V
Blancheteau
Alix
A
Delaguillaumie
Frédérique
F
Michel
Stéphane
S
Bécart
Giovanna
G
Lombardi
Oreste
O
Acuto
Dominique
D
Charron
Nuala
N
Mooney
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells; D017209:Apoptosis / Q000276:immunology*; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins; D008564:Membrane Potentials; D051379:Mice; D008928:Mitochondria; D010446:Peptide Fragments / Q000276:immunology*; D010718:Phosphatidylserines / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D010718:Phosphatidylserines; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor; D020169:Caspases