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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.

Original publication

DOI

10.1189/jlb.0703356

Type

Journal article

Journal

J Leukoc Biol

Publication Date

06/2004

Volume

75

Pages

1036 - 1044

Keywords

Animals, Antigen Presentation, Antigen-Presenting Cells, Apoptosis, Caspases, Enzyme Activation, Fas Ligand Protein, Histocompatibility Antigens Class II, Humans, Interleukin-2, Lymphocyte Activation, Membrane Glycoproteins, Membrane Potentials, Mice, Mitochondria, Peptide Fragments, Phosphatidylserines, Receptors, Antigen, T-Cell, T-Lymphocytes, fas Receptor