Lopez, DanielGarcía-Calvo, MargaritaSmith, Geoffrey LDel Val, Margarita2019-11-212019-11-212010-05-01J Immunol. 2010 May 1;184(9):5193-9. doi: 10.4049/jimmunol.1000050. Epub 2010 Mar 26.0022-1767http://hdl.handle.net/20.500.12105/8630CD8(+) cytotoxic T lymphocytes recognize infected cells in which MHC class I molecules present pathogen-derived peptides that have been processed mainly by proteasomes. Many infections induce a set of proteases, the caspases involved in apoptosis or inflammation. In this study, we report that processing and presentation of a short vaccinia virus-encoded Ag can take place also by a nonproteasomal pathway, which was blocked in infected cells with chemical inhibitors of caspases. By cleaving at noncanonical sites, at least two caspases generated antigenic peptides recognized by T lymphocytes. The sites and the peptidic products were partially overlapping but different to those used and produced by proteasomes in vitro. Antigenic natural peptides produced in infected cells by either pathway were quantitatively and qualitatively similar. Finally, coexpression of the natural vaccinia virus protein B13, which is an inhibitor of caspases and apoptosis, impaired Ag presentation by the caspase pathway in infected cells. These data support the hypothesis that numerous cellular proteolytic systems, including those induced during infection, such as caspases involved in apoptosis or in inflammation, contribute to the repertoire of presented peptides, thereby facilitating immunosurveillance.engAMhttp://creativecommons.org/licenses/by-nc-nd/4.0/Amino Acid SequenceAnimalsAntigen PresentationApoptosisCD8-Positive T-LymphocytesCaspasesCell LineH-2 AntigensHistocompatibility Antigen H-2DImmediate-Early ProteinsImmunodominant EpitopesMiceMice, Inbred BALB CMolecular Sequence DataMuromegalovirusPeptidesProteasome Endopeptidase ComplexSignal TransductionVaccinia virusAttribution-NonCommercial-NoDerivatives 4.0 Internacional2034842618495193-910.4049/jimmunol.10000501550-6606Journal of immunology (Baltimore, Md. : 1950)open access