{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:58:22Z","timestamp":1781107102663,"version":"3.54.1"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,11,12]]},"abstract":"<jats:p>\n                    Studies in melanoma patients have revealed that self proteins can function as targets for tumor-reactive cytotoxic T lymphocytes (CTL). One group of self proteins MAGE, BAGE, and GAGE are normally only expressed in testis and placenta, whilst another group of CTL recognized proteins are melanocyte-specific differentiation antigens. In this study we have investigated whether CTL can be raised against a ubiquitously expressed self protein, mdm-2, which is frequently overexpressed in tumors. The observation that T-cell tolerance is self major histocompatibility complex-restricted was exploited to generate CTL specific for an mdm-2 derived peptide presented by nonself major histocompatibility complex class I molecules. Thus, the allo-restricted T-cell repertoire of H-2\n                    <jats:sup>d<\/jats:sup>\n                    mice was used to isolate CTL specific for the mdm100 peptide presented by allogeneic H-2K\n                    <jats:sup>b<\/jats:sup>\n                    class I molecules.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , these CTL discriminated between transformed and normal cells, killing specifically K\n                    <jats:sup>b<\/jats:sup>\n                    -positive melanoma and lymphoma tumors but not K\n                    <jats:sup>b<\/jats:sup>\n                    -expressing dendritic cells.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , the CTL showed antitumor activity and delayed the growth of melanoma as well as lymphoma tumors in H-2\n                    <jats:sup>b<\/jats:sup>\n                    recipient mice. These experiments show that it is possible to circumvent T-cell tolerance to ubiquitously expressed self antigens, and to target CTL responses against tumors expressing elevated levels of structurally unaltered proteins.\n                  <\/jats:p>","DOI":"10.1073\/pnas.93.23.13114","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:16Z","timestamp":1027679656000},"page":"13114-13118","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":104,"title":["Peptide-specific cytotoxic T lymphocytes restricted by nonself major histocompatibility complex class I molecules: Reagents for tumor\u2009immunotherapy"],"prefix":"10.1073","volume":"93","author":[{"given":"Elena","family":"Sadovnikova","sequence":"first","affiliation":[{"name":"Department of Immunology, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Stauss","sequence":"additional","affiliation":[{"name":"Department of Immunology, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,11,12]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.3.725"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1840703"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(95)80053-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.3.689"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.2.489"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.1.35"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.9.3515"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.3.1005"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7513441"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.7a.1126"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.9.2617.2617"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910570311"},{"key":"e_1_3_2_13_2","first-page":"1699","volume":"6","author":"Bartek J","year":"1991","unstructured":"J Bartek, J Bartkova, B Vojtesek, Z Staskova, J Lukas, A Rejthar, J Kovarik, C A Midgley, J V Gannon, D P Lane Oncogene 6, 1699\u20131703 (1991).","journal-title":"Oncogene"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.4049\/jimmunol.157.1.239","volume":"157","author":"Dahl A M","year":"1996","unstructured":"A M Dahl, P Beverley, H J Stauss J Immunol 157, 239\u2013246 (1996).","journal-title":"J Immunol"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/308738a0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/308741a0"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.162.6.1745"},{"key":"e_1_3_2_18_2","first-page":"11669","volume":"267","author":"Yang Y","year":"1992","unstructured":"Y Yang, K Fr\u00fch, J Chambers, J B Waters, L Wu, T Spies, P A Peterson J Immunol 267, 11669\u201311672 (1992).","journal-title":"J Immunol"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/57.5.1199"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00375866"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/6.2.289"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.169.4.1255"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.09.040191.001415"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb07676.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.26.11993"},{"key":"e_1_3_2_26_2","first-page":"133","volume":"1","author":"Goldman J M","year":"1989","unstructured":"J M Goldman Bone Marrow Transplant 1, 133\u2013134 (1989).","journal-title":"Bone Marrow Transplant"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.23.13114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T08:12:39Z","timestamp":1682151159000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.23.13114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,11,12]]},"references-count":26,"journal-issue":{"issue":"23","published-print":{"date-parts":[[1996,11,12]]}},"alternative-id":["10.1073\/pnas.93.23.13114"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.23.13114","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,11,12]]},"assertion":[{"value":"1996-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1996-08-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1996-11-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}