title: Modification of Antigen Impacts on Memory Quality after Adenovirus Vaccination.
abstract: The establishment of robust T cell memory is critical for the development of novel vaccines for infections and cancers. Classical memory generated by CD8(+)T cells is characterized by contracted populations homing to lymphoid organs. T cell memory inflation, as seen for example after CMV infection, is the maintenance of expanded, functional, tissue-associated effector memory cell pools. Such memory pools may also be induced after adenovirus vaccination, and we recently defined common transcriptional and phenotypic features of these populations in mice and humans. However, the rules that govern which epitopes drive memory inflation compared with classical memory are not fully defined, and thus it is not currently possible to direct this process. We used our adenoviral model of memory inflation to first investigate the role of the promoter and then the role of the epitope context in determining memory formation. Specifically, we tested the hypothesis that conventional memory could be converted to inflationary memory by simple presentation of the Ag in the form of minigene vectors. When epitopes from LacZ and murine CMV that normally induce classical memory responses were presented as minigenes, they induced clear memory inflation. These data demonstrate that, regardless of the transgene promoter, the polypeptide context of a CD8(+)T cell epitope may determine whether classical or inflating memory responses are induced. The ability to direct this process by the use of minigenes is relevant to the design of vaccines and understanding of immune responses to pathogens.
authors.affiliation: Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kingdom; and jcolston@doctors.org.uk paul.klenerman@medawar.ox.ac.uk.
authors.forename: Julia M
authors.identifier: http://orcid.org/0000-0002-3337-2455
authors.initials: JM
authors.lastname: Colston
authors.affiliation: Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kingdom; and.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bolinger
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kindgom.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Cottingham
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kindgom.
authors.forename: Sarah
authors.identifier: http://orcid.org/0000-0002-6823-9750
authors.initials: S
authors.lastname: Gilbert
authors.affiliation: Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kingdom; and jcolston@doctors.org.uk paul.klenerman@medawar.ox.ac.uk.
authors.forename: Paul
authors.identifier: http://orcid.org/0000-0003-4307-9161
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory / Q000276:immunology*; D007763:Lac Operon / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D014611:Vaccination
chemical_list: D000941:Antigens; D018984:Epitopes, T-Lymphocyte