학술논문

Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection.
Document Type
Article
Source
Nature Medicine. Dec2007, Vol. 13 Issue 12, p1431-1439. 9p. 1 Chart, 5 Graphs.
Subject
*HIV infections
*LYMPHOCYTES
*T cells
*EPITOPES
*APOPTOSIS
*CELL death
*DENDRITIC cells
*LYMPHOID tissue
Language
ISSN
1078-8956
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. [ABSTRACT FROM AUTHOR]