{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T16:00:59Z","timestamp":1782316859772,"version":"3.54.5"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":2381,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tick-borne encephalitis virus (TBEV) is a leading cause of viral meningoencephalitis in many parts of Europe and eastwards in Asia, with high morbidity and often long-term neurologic sequelae. With no treatment available, studies of the immune response to TBEV are essential for the understanding of the immunopathogenesis of tick-borne encephalitis and for the development of therapeutics. We have previously demonstrated that CD8+ T cell responses in peripheral blood in patients with acute TBEV peak at around 7 d after hospitalization in the neuroinvasive phase of the disease. In this study, we identified six novel TBEV HLA-A2\u2013 and HLA-B7\u2013restricted epitopes, all derived from the nonstructural proteins of TBEV. This identification allowed for a comprehensive phenotypic and temporal analysis of the HLA-A2\u2013 and HLA-B7\u2013restricted Ag-specific CD8+ T cell response during the acute stages of human TBEV infection. HLA-A2\u2013 and HLA-B7\u2013restricted TBEV epitope\u2013specific effector cells predominantly displayed a CD45RA\u2212CCR7\u2212CD27+CD57\u2212 phenotype at day 7, which transitioned into separate distinct phenotypes for HLA-A2\u2013 and HLA-B7\u2013restricted TBEV-specific CD8+ T cells, respectively. At day 21, the most prevalent phenotype in the HLA-A2\u2013restricted CD8+ T cell populations was CD45RA\u2212CCR7\u2212CD27+CD57+, whereas the HLA-B7\u2013restricted CD8+ T cell population was predominantly CD45RA+CCR7\u2212CD27+CD57+. Almost all TBEV epitope\u2013specific CD8+ T cells expressed \u03b14 and \u03b21 integrins at days 7 and 21, whereas the bulk CD8+ T cells expressed lower integrin levels. Taken together, human TBEV infection elicits broad responses to multiple epitopes, predominantly derived from the nonstructural part of the virus, establishing distinct maturation patterns for HLA-A2\u2013 and HLA-B7\u2013restricted TBEV epitope\u2013specific CD8+ T cells.<\/jats:p>","DOI":"10.4049\/immunohorizons.1800029","type":"journal-article","created":{"date-parts":[[2018,7,2]],"date-time":"2018-07-02T19:45:18Z","timestamp":1530560718000},"page":"172-184","source":"Crossref","is-referenced-by-count":19,"title":["Breadth and Dynamics of HLA-A2\u2013 and HLA-B7\u2013Restricted CD8+ T Cell Responses against Nonstructural Viral Proteins in Acute Human Tick-Borne Encephalitis Virus Infection"],"prefix":"10.1093","volume":"2","author":[{"given":"Margit H","family":"Lampen","sequence":"first","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital , 141 86 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"Uchtenhagen","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medicine, Solna, Karolinska Institutet , 10450 Stockholm ,","place":["Sweden"]},{"name":"Division of Infectious Diseases, Karolinska University Hospital Solna , 171 76 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Blom","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital , 141 86 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Varnait\u0117","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital , 141 86 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3252-3901","authenticated-orcid":false,"given":"Jolita","family":"Pakalniene","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Medical Academy, Lithuanian University of Health Sciences , 47116 Kaunas ,","place":["Lithuania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Dailidyte","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Medical Academy, Lithuanian University of Health Sciences , 47116 Kaunas ,","place":["Lithuania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5869-1746","authenticated-orcid":false,"given":"S\u00e9bastien","family":"W\u00e4lchli","sequence":"additional","affiliation":[{"name":"Section for Cellular Therapy, Department of Oncology, Oslo University Hospital , 0379 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3530-7382","authenticated-orcid":false,"given":"Lars","family":"Lindquist","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Karolinska University Hospital , 14186 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aukse","family":"Mickiene","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Medical Academy, Lithuanian University of Health Sciences , 47116 Kaunas ,","place":["Lithuania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6948-7281","authenticated-orcid":false,"given":"Jakob","family":"Micha\u00eblsson","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital , 141 86 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton N","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Division of Molecular Oncology and Immunology, Netherlands Cancer Institute , 1066 CX Amsterdam , the","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Gustaf","family":"Ljunggren","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital , 141 86 Stockholm ,","place":["Sweden"]},{"name":"Department of Infectious Diseases, Karolinska University Hospital , 14186 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6275-0750","authenticated-orcid":false,"given":"Johan K","family":"Sandberg","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital , 141 86 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0432-710X","authenticated-orcid":false,"given":"Adnane","family":"Achour","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medicine, Solna, Karolinska Institutet , 10450 Stockholm ,","place":["Sweden"]},{"name":"Division of Infectious Diseases, Karolinska University Hospital Solna , 171 76 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2446-4323","authenticated-orcid":false,"given":"Sara","family":"Gredmark-Russ","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital , 141 86 Stockholm ,","place":["Sweden"]},{"name":"Department of Infectious Diseases, Karolinska 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