Apoptosis of the APC is concurrent with successful antigen presentation

Vincent Blancheteau, Frederique Michel, Oreste Acuto, Robert Lechler, Dominique Charron, Giovanna Lombardi, Nuala A Mooney

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    Apoptosis of both B lymphocytes and mature dendritic cells has been documented as a consequence of activation of the APC via HLA-DR. These data raised the question of whether the physiological role of HLA-DR, ie peptide presentation to a specific TCR, could actually induce apoptosis of the APC. We have addressed this question using MHC class II restricted peptide specific T cell clones. In the first instance a non-cytotoxic murine T cell hybridoma T8.1, expressing a chimeric human/murine TCR and human CD4 and restricted by HLA DR11 and DR13 and specific for TT-(830-843) was examined. IL2 production was measured by ELISA concurrently with APC apoptosis detected by Annexin-V binding to APC which had been labelled with a vital dye (CMTMR) before beginning the co-culture. Apoptosis of the APC was detected (40% specific apoptosis) only when successful presentation had occurred as assessed by IL-2 production. Co-culture of T8.1 with either an irrelevant peptide or an APC expressing an irrelevant HLA-DR failed to induce apoptosis of the APC. We also examined a human T cell clone which is specific for HA-(307-319) and restricted by HLA-DR7, APC apoptosis was even more marked in this system (70% specific apoptosis), only occurred in the presence of relevant peptide and was only partially inhibited in the presence of an antagonist CD95 mAb. Taken together these data provide evidence that: peptide presentation is not anodyne for the APC, the demise of the APC is concurrent with peptide presentation and MHC class II mediated apoptosis could provide a means of limiting the immune response.
    Original languageEnglish
    Pages (from-to)A1021
    JournalFaseb Journal
    Issue number5
    Publication statusPublished - 2001


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