Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection.

TitleCross-presentation of caspase-cleaved apoptotic self antigens in HIV infection.
Publication TypeJournal Article
Year of Publication2007
AuthorsRawson, PMoroni, Molette, C, Videtta, M, Altieri, L, Franceschini, D, Donato, T, Finocchi, L, Propato, A, Paroli, M, Meloni, F, Mastroianni, CM, d'Ettorre, G, Sidney, J, Sette, A, Barnaba, V
JournalNat Med
Volume13
Issue12
Pagination1431-9
Date Published2007 Dec
ISSN1546-170X
KeywordsAdult, Antigen Presentation, Apoptosis, Caspases, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytoskeleton, Dendritic Cells, Epitopes, Female, HIV Infections, Humans, Male, Middle Aged, Vimentin
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.

DOI10.1038/nm1679
Alternate JournalNat. Med.
PubMed ID18026114