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Here, we identified CD80 as a cell surface antigen highly expressed in EBV-positive B-cell lymphomas. Monoclonal antibodies were generated from mice immunized with recombinant human CD80 and subsequently engineered into chimeric formats. These antibodies were evaluated for their cytotoxic activity against CD80-expressing lymphoma cells. Notably, high-affinity clones elicited robust antibody-dependent cellular cytotoxicity (ADCC) but lacked complement-dependent cytotoxicity (CDC), in contrast to rituximab, which targets CD20 and mediates both ADCC and CDC. Our findings suggest that cytotoxic effector functions are regulated not only by the constant region of the antibody but also by the antigen recognized by its variable region. Importantly, these CD80-specific antibodies do not inhibit T cell responses against EBV-positive immortalized cells, highlighting their potential as promising therapeutic candidates for EBV-positive lymphomas and other CD80-expressing malignancies.<\/jats:p>","DOI":"10.1038\/s41598-026-55043-5","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T09:16:17Z","timestamp":1779786977000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD80 (B7-1) as a potential therapeutic target in Epstein\u2013Barr virus\u2011associated B cell diseases"],"prefix":"10.1038","volume":"16","author":[{"given":"Rin","family":"Yoshizato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Tamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Kawano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Hokama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanami","family":"Soda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusei","family":"Ota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotomi","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taisei","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Ishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouichi","family":"Ohga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoharu","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"55043_CR1","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/s41564-018-0334-0","volume":"4","author":"Y Okuno","year":"2019","unstructured":"Okuno, Y. et al. 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