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Cytotoxic T cells bearing BCMA-specific T-cell receptors might further allow targeting HLA-presented antigens derived from the intracellular domain of BCMA. By analyzing a mass spectrometry-acquired immunopeptidome dataset of primary MM samples and MM cell lines for BCMA-derived HLA ligands, we identified the naturally presented HLA-B*18-restricted ligand P(BCMA)<jats:sub>B*18<\/jats:sub>. Additionally, P(BCMA)<jats:sub>B*18<\/jats:sub> was identified on primary CLL samples, thereby expanding the range for possible applications. P(BCMA)<jats:sub>B*18<\/jats:sub> induced multifunctional BCMA-specific cells de novo from na\u00efve CD8<jats:sup>+<\/jats:sup> T cells of healthy volunteers. These T cells exhibited antigen-specific lysis of autologous peptide-loaded cells. Even in the immunosuppressive context of MM, we detected spontaneous memory T-cell responses against P(BCMA)<jats:sub>B*18<\/jats:sub> in patients. By applying CTLA-4 and PD-1 inhibition in vitro we induced multifunctional P(BCMA)<jats:sub>B*18<\/jats:sub>-specific CD8<jats:sup>+<\/jats:sup> T cells in MM patients lacking preexisting BCMA-directed immune responses. Finally, we could show antigen-specific lysis of autologous peptide-loaded target cells and even MM.1S cells naturally presenting P(BCMA)<jats:sub>B*18<\/jats:sub> using patient-derived P(BCMA)<jats:sub>B*18<\/jats:sub>-specific T cells. Hence, this BCMA-derived T-cell epitope represents a promising target for T-cell-based immunotherapy and monitoring following immunotherapy in B-cell malignancy patients.<\/jats:p>","DOI":"10.1038\/s41408-020-0288-3","type":"journal-article","created":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T19:02:50Z","timestamp":1582916570000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8107-0419","authenticated-orcid":false,"given":"Tatjana","family":"Bilich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Nelde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Walz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Roerden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut R.","family":"Salih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Weisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Besemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Marcu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"L\u00fcbke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Schuhmacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian C.","family":"Neidert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Georg","family":"Rammensee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Stevanovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane S.","family":"Walz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,28]]},"reference":[{"key":"288_CR1","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1016\/S1470-2045(11)70243-1","volume":"12","author":"A Krishnan","year":"2011","unstructured":"Krishnan, A. et al. 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