{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:19:57Z","timestamp":1792120797105,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,6,28]],"date-time":"2008-06-28T00:00:00Z","timestamp":1214611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Objective:\u2002<\/jats:bold> The aim of this study is the identification of HLA\u2010A2 restricted T\u2010cell epitopes in the conserved region of the immunoglobulin\u2010G\u2010heavy\u2010chain (IgG<jats:sub>H<\/jats:sub>) that can be used for immunotherapy in multiple myeloma (MM) patients.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> After the IgG<jats:sub>H<\/jats:sub> gene sequence was scanned for HLA\u2010A2 restricted T\u2010cell epitopes with a high binding affinity to the MHC\u2010I\u2010complex, promising nona\u2010peptides were synthesized. Peptide specific CD8\u2003<jats:sup>+<\/jats:sup>\u2003 T\u2010cells were generated from peripheral blood mononuclear cells (PBMC) of healthy donors (HD) and patients with MM using peptide pulsed dendritic cells (DC) <jats:italic>in vitro.<\/jats:italic> The activation and cytotoxicity of CD8\u2003<jats:sup>+<\/jats:sup>\u2003 T\u2010cells was analyzed by IFN\u2010<jats:italic>\u03b1<\/jats:italic> ELISpot\u2010assay and <jats:sup>51<\/jats:sup>Chromium release\u2010assay. HLA\u2010A2 restriction was proven by blocking T\u2010cell activation with anti\u2010HLA\u2010A2 antibodies.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Two HLA\u2010A2 restricted T\u2010cell epitopes\u2013TLVTVSSAS derived from the IgG<jats:sub>H<\/jats:sub>\u2010framework\u2010region 4 (FR4) and LMISRTPEV from the constant region (CR)\u2010induced expansion of specific CD8\u2003<jats:sup>+<\/jats:sup>\u2003 T\u2010cells from PBMC in two of three (TLVTVSSAS) and one of three (LMISRTPEV) HD respectively. Specific T\u2010cells were induced from PBMC in two of six (TLVTVSSAS) and eight of 19 (LMISRTPEV) patients with MM<jats:italic>.<\/jats:italic> Specific CD8\u2003<jats:sup>+<\/jats:sup>\u2003 T\u2010cells also lysed peptide\u2010pulsed target cells in <jats:sup>51<\/jats:sup>Chromium release\u2010assay. LMISRTPEV specific CD8\u2003<jats:sup>+<\/jats:sup>\u2003T\u2010cells from MM patients lysed specifically the HLA\u2010A2\u2003<jats:sup>+<\/jats:sup>\u2003 IgG myeloma cell line XG\u20106.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> We identified two HLA\u2010A2 restricted T\u2010cell epitopes\u2013TLVTVSSAS and LMISRTPEV\u2013which can yield an expansion of CD8\u2003<jats:sup>+<\/jats:sup>\u2003 T\u2010cells with the ability to kill peptide\u2010loaded target cells and HLA\u2010A2\u2003<jats:sup>+<\/jats:sup>\u2003 IgG<jats:sup>+<\/jats:sup> myeloma cells. We conclude that TLVTVSSAS and LMISRTPEV could be T\u2010cell epitopes for immunotherapy in MM patients.<\/jats:p>","DOI":"10.1111\/j.1600-0609.2008.01076.x","type":"journal-article","created":{"date-parts":[[2008,3,19]],"date-time":"2008-03-19T13:50:54Z","timestamp":1205934654000},"page":"26-35","source":"Crossref","is-referenced-by-count":7,"title":["Identification of HLA\u2010A2 restricted T\u2010cell epitopes within the conserved region of the immunoglobulin G heavy\u2010chain in patients with multiple myeloma"],"prefix":"10.1111","volume":"81","author":[{"given":"Sebastian","family":"Belle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Condomines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Witzens\u2010Harig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Kasper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kleist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Terness","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Moos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"Cremer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Hose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony D.","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Goldschmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hundemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,6,28]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0073"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.6.2357"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2006.01.008"},{"key":"e_1_2_5_5_2","first-page":"1156","article-title":"Genes encoding tumor\u2010specific antigens are expressed in human myeloma cells","volume":"94","author":"Van Baren N","year":"1999","journal-title":"Blood"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-01-0366"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.5.1508"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200003)30:3<803::AID-IMMU803>3.0.CO;2-P"},{"key":"e_1_2_5_9_2","first-page":"598","article-title":"Immunotherapeutic strategies for the treatment of plasma cell malignancies","volume":"27","author":"Treon SP","year":"2000","journal-title":"Semin Oncol"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.5.3307"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.69.6.1540"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1996.419959.x"},{"key":"e_1_2_5_13_2","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1182\/blood.V91.7.2459","article-title":"Idiotype immunization combined with granulocyte\u2010macrophage colony\u2010stimulating factor in myeloma patients induced Type I, major histocompatibility complex\u2010restricted, CD8\u2010 and CD4\u2010specific T\u2010cell responses","volume":"91","author":"Osterborg A","year":"1998","journal-title":"Blood"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.2.673.414k30_673_683"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2000.01958.x"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.7.2411"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-06-1925"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403181"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/13928"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/76243"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.10.2999"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.12.3654.3654"},{"key":"e_1_2_5_23_2","doi-asserted-by":"crossref","first-page":"4727","DOI":"10.1182\/blood.V91.12.4727","article-title":"A gp130 interleukin\u20106 transducer\u2010dependent SCID model of human multiple myeloma","volume":"91","author":"Rebouissou C","year":"1998","journal-title":"Blood"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2006.11.002"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00172063"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.152.1.163"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401925"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002371-200203000-00001"},{"key":"e_1_2_5_29_2","first-page":"471","article-title":"Description of a novel FR1 IgH PCR strategy and its comparison with three other strategies for the detection of clonality in B\u2010cell malignancies","volume":"9","author":"Aubin J","year":"1995","journal-title":"Leukemia"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1990.tb02643.x"},{"key":"e_1_2_5_31_2","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1016\/S0021-9258(18)63134-5","article-title":"A crystallographic investigation of a human IgG immunoglobulin","volume":"245","author":"Edmundson AB","year":"1970","journal-title":"J Biol Chem"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(83)90057-3"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990301)80:5<671::AID-IJC7>3.0.CO;2-E"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1250"},{"key":"e_1_2_5_35_2","first-page":"957","article-title":"Idiotypic protein\u2010pulsed adherent peripheral blood mononuclear cell\u2010derived dendritic cells prime immune system in multiple myeloma","volume":"4","author":"Wen Y","year":"1998","journal-title":"Clin Cancer Res"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.thj.6200183"},{"key":"e_1_2_5_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.10.6168"},{"key":"e_1_2_5_38_2","first-page":"1337","article-title":"[The primary structure of a monoclonal IgA\u2010immunoglobulin (IgA Tro.), II. The amino acid sequence of the H\u2010chain, alpha\u2010type, subgroup III; structure of the complete IgA\u2010molecule (author\u2019s transl)]. [German]","volume":"356","author":"Kratzin HAP","year":"1975","journal-title":"Hoppe-Seylers Zeitschrift fur Physiologische Chemie"},{"key":"e_1_2_5_39_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.6.1750"},{"key":"e_1_2_5_40_2","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1182\/blood.V96.8.2828","article-title":"Tumor\u2010specific recognition of human myeloma cells by idiotype\u2010induced CD8(+) T\u2010cells","volume":"96","author":"Li Y","year":"2000","journal-title":"Blood"},{"key":"e_1_2_5_41_2","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1182\/blood.V95.4.1342.004k19_1342_1349","article-title":"Stimulation of cytotoxic T\u2010cells against idiotype immunoglobulin of malignant lymphoma with protein\u2010pulsed or idiotype\u2010transduced dendritic cells","volume":"95","author":"Osterroth F","year":"2000","journal-title":"Blood"},{"key":"e_1_2_5_42_2","first-page":"1139","article-title":"Idiotype vaccination of multiple myeloma patients using monocyte\u2010derived dendritic cells","volume":"88","author":"Reichardt VL","year":"2003","journal-title":"Haematologica"},{"key":"e_1_2_5_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.11.6631"},{"key":"e_1_2_5_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1076514"},{"key":"e_1_2_5_45_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050732"},{"key":"e_1_2_5_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1310"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1600-0609.2008.01076.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1600-0609.2008.01076.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T01:27:12Z","timestamp":1696987632000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1600-0609.2008.01076.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6,28]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,7]]}},"alternative-id":["10.1111\/j.1600-0609.2008.01076.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1600-0609.2008.01076.x","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6,28]]}}}