Sci. Signal., 27 April 2010
Antigen Presentation Processing by Caspases
John F. Foley
Science Signaling, AAAS, Washington, DC 20005, USA
When cells are infected, pathogen-derived proteins are processed by the proteasome, and the resultant peptides (after further processing) bind to the class I major histocompatibility complex (MHC) and are presented on the surface of the infected cell. CD8+ cytotoxic T lymphocytes (CTLs) recognize these peptide-MHC complexes and kill the infected cell. Noting that viral infection often activates caspases, cytosolic cysteine proteases that trigger apoptosis, López et al. investigated whether caspases might also contribute to antigen presentation. The authors infected murine cells with recombinant vaccinia virus (rVACV) that expressed a miniprotein (m19) and cultured the cells with CTL lines specific for an epitope within m19. The CTLs killed the infected cells and also killed infected cells that were incubated with either a proteasome-specific inhibitor or a caspase-specific inhibitor; however, treatment of the infected cells with both inhibitors blocked killing by the CTLs. Analysis of peptide products from in vitro assays showed that human recombinant caspases 5 and 10 cleaved m19 at noncanonical sites to generate the antigenic epitope that activated the CTLs. Within infected murine cells, caspases and the proteasome independently generated similar antigenic peptides in sufficient quantities to activate CTLs. When cells were infected with an rVACV that expressed B13, a protein that blocks caspase activation, only blockade of the proteasome was required to inhibit the presentation of antigen to CTLs. Together, these data suggest that the activation of caspases in response to viral infection contributes to the range of antigenic peptides presented by the infected cell.
D. López, M. García-Calvo, G. L. Smith, M. Del Val, Caspases in virus-infected cells contribute to recognition by CD8+ T lymphocytes. J. Immunol. 184, 5193–5199 (2010). [PubMed]
Citation: J. F. Foley, Processing by Caspases. Sci. Signal. 3, ec125 (2010).
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