Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection
2007
Moroni Rawson, Pisana | Molette, Caroline | Videtta, Melissa | Altieri, Laura | Franceschini, Debora | Donato, Tiziana | Finocchi, Luigi | Propato, Antonella | Paroli, Marino | Meloni, Francesca | Mastroianni, Claudio M. | d'Ettorre, Gabriella | Sidney, John | Sette, Alessandro | Barnaba, Vincenzo | Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome] (UNIROMA) | La Jolla Institute for Immunology [La Jolla, CA, États-Unis] | Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti ; Pasteur Network (Réseau International des Instituts Pasteur)
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Show more [+] Less [-]English. We found that the proteome of apoptotic T cells includes prominent fragments of cellular proteins generated by caspases and that a high proportion of distinct T cell epitopes in these fragments is recognized by CD8+ T cells during HIV infection. The frequencies of effector CD8+ T cells that are specific for apoptosis-dependent epitopes correlate with the frequency of circulating apoptotic CD4+ T cells in HIV-1–infected individuals. We propose that these self-reactive effector CD8+ T cells may contribute to the systemic immune activation during chronic HIV infection. The caspase-dependent cleavage of proteins associated with apoptotic cells has a key role in the induction of self-reactive CD8+ T cell responses, as the caspase-cleaved fragments are efficiently targeted to the processing machinery and are cross-presented by dendritic cells. These findings demonstrate a previously undescribed role for caspases in immunopathology.
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