title: Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection.
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.
authors.affiliation: Fondazione Andrea Cesalpino-Dipartimento di Medicina Interna, Sapienza Università di Roma, 00161 Rome, Italy.
authors.forename: Pisana Moroni
authors.initials: PM
authors.lastname: Rawson
authors.forename: Caroline
authors.initials: C
authors.lastname: Molette
authors.forename: Melissa
authors.initials: M
authors.lastname: Videtta
authors.forename: Laura
authors.initials: L
authors.lastname: Altieri
authors.forename: Debora
authors.initials: D
authors.lastname: Franceschini
authors.forename: Tiziana
authors.initials: T
authors.lastname: Donato
authors.forename: Luigi
authors.initials: L
authors.lastname: Finocchi
authors.forename: Antonella
authors.initials: A
authors.lastname: Propato
authors.forename: Marino
authors.initials: M
authors.lastname: Paroli
authors.forename: Francesca
authors.initials: F
authors.lastname: Meloni
authors.forename: Claudio M
authors.initials: CM
authors.lastname: Mastroianni
authors.forename: Gabriella
authors.initials: G
authors.lastname: d'Ettorre
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barnaba
mesh_terms: D000328:Adult; D017951:Antigen Presentation; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D020169:Caspases / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000737:chemistry; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D014746:Vimentin / Q000737:chemistry
chemical_list: D000939:Epitopes; D014746:Vimentin; D020169:Caspases