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Article
Nature Medicine 13, 1431 - 1439 (2007)
Published online: 18 November 2007 | doi:10.1038/nm1679
Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection
Pisana Moroni Rawson1,5,6, Caroline Molette1,5,6, Melissa Videtta1, Laura Altieri1, Debora Franceschini1, Tiziana Donato1, Luigi Finocchi1, Antonella Propato1, Marino Paroli1, Francesca Meloni1, Claudio M Mastroianni2, Gabriella d'Ettorre2, John Sidney3, Alessandro Sette3 & Vincenzo Barnaba1,4
Abstract
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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