{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:41:33Z","timestamp":1789656093481,"version":"4.0.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>\n                      In our previous work, a total of 103 CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell epitopes restricted by 13 prevalent HLA-A allotypes in Northeast Asians were validated from the main proteins of hepatitis B virus (HBV). This study aims to further screen the T-cell epitopes restricted by 15 prevalent HLA-B and 14 prevalent HLA-C allotypes and establish a universal assay for counting reactive HBV-specific T cells in patients with chronic hepatitis B (CHB).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell epitopes were systematically screened through a combination of\n                      <jats:italic>in silico<\/jats:italic>\n                      prediction,\n                      <jats:italic>ex vivo<\/jats:italic>\n                      co-cultures of peptides with patient-derived peripheral blood mononuclear cells (PBMCs), and peptide competitive binding assays using HLA-B\/C transfected cell lines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 89 novel CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell epitopes were identified from four HBV main proteins using PBMCs from 250 CHB patients. Furthermore, 201 validated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell epitope peptides restricted by the 13 HLA-A, 15 HLA-B, and 14 HLA-C allotypes were integrated to construct a broad-spectrum epitope peptide library, and by which the ELISpot assay was established followed by clinical testing for 81 CHB patients. The counts of reactive HBV-specific T cells and T cells reactive to each HBV protein (HBsAg-, HBpol-, HBx-, or HBeAg-) in PBMCs showed a negative correlation with serum HBsAg levels and no correlation with HBeAg or ALT levels. NUCs\/IFN-\u03b1 combination elicited significantly more reactive HBV-specific T cells (including those targeting HBsAg, HBpol, HBx, or HBeAg) than NUCs or IFN-\u03b1 monotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The proposed method holds great potential for facilitating routine evaluation of HBV-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell reactivity in CHB patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1717543","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:40:15Z","timestamp":1767940815000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Large-scale screening of HBV epitopes restricted by multiple prevalent HLA-B\/C allotypes and routine detection of HBV-specific T cells in CHB patients"],"prefix":"10.3389","volume":"16","author":[{"given":"Yandan","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixue","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangping","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanlai","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/S2468-1253(22)00124-8","article-title":"Global, 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