{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T04:27:06Z","timestamp":1745382426900,"version":"3.37.3"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":1832,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CD4+ helper T cells play important roles in providing help to B cells, macrophages, and cytotoxic CD8+ T cells, but also exhibit direct effector functions against a variety of different pathogens. In contrast to CD8+ T cells, CD4+ T cells typically exhibit broader specificities and undergo less clonal expansion during many types of viral infections, which often makes the identification of virus-specific CD4+ T cells technically challenging. In this study, we have generated recombinant vaccinia virus (VacV) vectors that target I-Ab\u2013restricted peptides for MHC class II (MHC-II) presentation to activate CD4+ T cells in mice. Conjugating the lymphocytic choriomeningitis virus immunodominant epitope GP61\u201380 to either LAMP1 to facilitate lysosomal targeting or to the MHC-II invariant chain (Ii) significantly increased the activation of Ag-specific CD4+ T cells in vivo. Immunization with VacV-Ii-GP61\u201380 activated endogenous Ag-specific CD4+ T cells that formed memory and rapidly re-expanded following heterologous challenge. Notably, immunization of mice with VacV expressing an MHC-II\u2013restricted peptide from Leishmania species (PEPCK335\u2013351) conjugated to either LAMP1 or Ii also generated Ag-specific memory CD4+ T cells that underwent robust secondary expansion following a visceral leishmaniasis infection, suggesting this approach could be used to generate Ag-specific memory CD4+ T cells against a variety of different pathogens. Overall, our data show that VacV vectors targeting peptides for MHC-II presentation is an effective strategy to activate Ag-specific CD4+ T cells in vivo and could be used to study Ag-specific effector and memory CD4+ T cell responses against a variety of viral, bacterial, or parasitic infections.<\/jats:p>","DOI":"10.4049\/immunohorizons.1900070","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T00:55:11Z","timestamp":1578012911000},"page":"1-13","source":"Crossref","is-referenced-by-count":4,"title":["Vaccinia Virus Vectors Targeting Peptides for MHC Class II Presentation to CD4+ T Cells"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4282-8813","authenticated-orcid":false,"given":"Samuel J","family":"Hobbs","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Oregon Health & Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2485-3932","authenticated-orcid":false,"given":"Jake C","family":"Harbour","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Oregon Health & Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2016-9789","authenticated-orcid":false,"given":"Phillip A","family":"Yates","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Oregon Health & Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6492-8842","authenticated-orcid":false,"given":"Diana","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Oregon Health & Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1643-6664","authenticated-orcid":false,"given":"Scott M","family":"Landfear","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Oregon Health & Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey C","family":"Nolz","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Oregon Health & Science University , Portland, OR 97239"},{"name":"Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University , Portland, OR 97239"},{"name":"Department of Radiation Medicine, Oregon Health & Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,1,3]]},"reference":[{"key":"2025010608420700000_r1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.immuni.2009.05.001","article-title":"Plasticity of CD4+ T cell lineage differentiation","volume":"30","author":"Zhou","year":"2009","journal-title":"Immunity"},{"key":"2025010608420700000_r2","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.1178334","article-title":"Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells","volume":"327","author":"O\u2019Shea","year":"2010","journal-title":"Science"},{"key":"2025010608420700000_r3","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev-immunol-030409-101212","article-title":"Differentiation of effector CD4 T cell populations (*)","volume":"28","author":"Zhu","year":"2010","journal-title":"Annu. 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