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Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors.

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dc.date 2018-02-21T20:25:13Z
dc.date 2018-02-21T20:25:13Z
dc.date 2016-12
dc.date.accessioned 2018-04-18T10:54:02Z
dc.date.available 2018-04-18T10:54:02Z
dc.identifier http://hdl.handle.net/20.500.11810/4606
dc.identifier 10.1371/journal.ppat.1006072
dc.identifier.uri http://hdl.handle.net/20.500.11810/4606
dc.description Cytomegalovirus (CMV) elicits long-term T-cell immunity of unparalleled strength, which has allowed the development of highly protective CMV-based vaccine vectors. Counterintuitively, experimental vaccines encoding a single MHC-I restricted epitope offered better immune protection than those expressing entire proteins, including the same epitope. To clarify this conundrum, we generated recombinant murine CMVs (MCMVs) encoding well-characterized MHC-I epitopes at different positions within viral genes and observed strong immune responses and protection against viruses and tumor growth when the epitopes were expressed at the protein C-terminus. We used the M45-encoded conventional epitope HGIRNASFI to dissect this phenomenon at the molecular level. A recombinant MCMV expressing HGIRNASFI on the C-terminus of M45, in contrast to wild-type MCMV, enabled peptide processing by the constitutive proteasome, direct antigen presentation, and an inflation of antigen-specific effector memory cells. Consequently, our results indicate that constitutive proteasome processing of antigenic epitopes in latently infected cells is required for robust inflationary responses. This insight allows utilizing the epitope positioning in the design of CMV-based vectors as a novel strategy for enhancing their efficacy.
dc.language en
dc.subject Research Subject Categories::MEDICINE
dc.subject Cytomegalovirus
dc.subject Immunity
dc.subject Vaccine development
dc.title Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors.
dc.type Journal Article


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