|Title||Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection.|
|Publication Type||Journal Article|
|Year of Publication||2007|
|Authors||Rawson, 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|
|Date Published||2007 Dec|
|Keywords||Adult, Antigen Presentation, Apoptosis, Caspases, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytoskeleton, Dendritic Cells, Epitopes, Female, HIV Infections, Humans, Male, Middle Aged, Vimentin|
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.
|Alternate Journal||Nat. Med.|