Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection.
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.
Rawson
Pisana Moroni
PM
Fondazione Andrea Cesalpino-Dipartimento di Medicina Interna, Sapienza Università di Roma, 00161 Rome, Italy.
Molette
Caroline
C
Videtta
Melissa
M
Altieri
Laura
L
Franceschini
Debora
D
Donato
Tiziana
T
Finocchi
Luigi
L
Propato
Antonella
A
Paroli
Marino
M
Meloni
Francesca
F
Mastroianni
Claudio M
CM
d'Ettorre
Gabriella
G
Sidney
John
J
Sette
Alessandro
A
Barnaba
Vincenzo
V
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
D000939:Epitopes; D014746:Vimentin; D020169:Caspases