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It is only during immunocompromise and especially impaired CD4<jats:sup>+<\/jats:sup>T cell function in the brain, as seen in AIDS patients or natalizumab-treated multiple sclerosis patients, that JCV may cause progressive multifocal leukoencephalopathy (PML), an often life-threatening brain disease. Since CD4<jats:sup>+<\/jats:sup>T cells likely play an important role in controlling JCV infection, we here describe the T cell response to JCV in a group of predominantly HLA-DR-heterozygotic healthy donors (HD) by using a series of overlapping 15-mer peptides spanning all JCV-encoded open reading frames. We identified immunodominant epitopes and compared T cell responses with anti-JCV VP1 antibody production and with the presence of urinary viral shedding. We observed positive JCV-specific T cell responses in 28.6% to 77.6%, humoral immune response in 42.6% to 89.4%, and urinary viral shedding in 36.4% to 45.5% of HD depending on the threshold. Four immunodominant peptides were mapped, and at least one immunogenic peptide per HLA-DRB1 allele was detected in DRB1*01<jats:sup>+<\/jats:sup>, DRB1*07<jats:sup>+<\/jats:sup>, DRB1*11<jats:sup>+<\/jats:sup>, DRB1*13<jats:sup>+<\/jats:sup>, DRB1*15<jats:sup>+<\/jats:sup>, and DRB1*03<jats:sup>+<\/jats:sup>individuals. We show for the first time that JCV-specific T cell responses may be directed not only against JCV VP1 and large T antigen but also against all other JCV-encoded proteins. Heterozygotic DRB1*04:01<jats:sup>+<\/jats:sup>individuals showed very low T cell responses to JCV together with normal anti-VP1 antibody levels and no urinary viral shedding, indicating a dominant-negative effect of this allele on global JCV-directed T cell responses. Our data are potentially relevant for the development of vaccines against JCV.<\/jats:p>","DOI":"10.1128\/jvi.02803-12","type":"journal-article","created":{"date-parts":[[2013,1,10]],"date-time":"2013-01-10T14:19:39Z","timestamp":1357827579000},"page":"3393-3408","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["T Cell Epitope Mapping of JC Polyoma Virus-Encoded Proteome Reveals Reduced T Cell Responses in HLA-DRB1*04:01<sup>+<\/sup>Donors"],"prefix":"10.1128","volume":"87","author":[{"given":"Ilijas","family":"Jel\u010di\u0107","sequence":"first","affiliation":[{"name":"Institute for Neuroimmunology and Clinical MS Research (inims), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany"},{"name":"Department of Neuroimmunology and MS Research, Neurology Clinic, University Hospital Z\u00fcrich, Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilian","family":"Aly","sequence":"additional","affiliation":[{"name":"Institute for Neuroimmunology and Clinical MS Research (inims), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M. 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