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

External protocol Created on 03 May 2014

Authors

Pisana Moroni Rawson, Caroline Molette, Melissa Videtta, Alessandro Sette, Laura Altieri, Debora Franceschini, Tiziana Donato, Marino Paroli, Francesca Meloni, John Sidney, and Vincenzo Barnaba

Summary

Apoptotic cells, via the activation of caspases, undergo significant proteome alterations. Phagocytosis of apoptotic cells by dendritic cells (DCs) leads to the processing of the apoptotic cell-associated (apoptotic) antigens and the cross-presentation of the resulting peptides on major histocompatibility complex class I molecules. This phenomenon seems crucial for inducing either cross-priming or cross-tolerance of CD8+ T cells, based on the presence or absence of various infectious or danger signals influencing the switch from tolerogenic immature DCs (iDCs) to mature DCs (mDCs) with high stimulatory and migratory capacities. Here, we demonstrate the following: (a) the protein modifications in apoptotic T cells, as detected by comparing the proteomic profiles of apoptotic and nonapoptotic T cells, generate apoptotic proteins that have antigenic properties with respect to human CD8+ T cells; (b) these autoreactive CD8+ T cell responses correlate with the proportion of apoptotic CD4+ T cells in individuals with HIV infection in vivo and contribute to chronic immune activation; and (c) the caspase-mediated cleavage of several cellular components during apoptosis facilitates antigen processing and cross-presentation by Dcs.

Further details

The protocol was published on Protocol Exchange in 2007. To see the entire protocol, click on the source link.

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