{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:22:36Z","timestamp":1790518956264,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2002,8,1]],"date-time":"2002-08-01T00:00:00Z","timestamp":1028160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2002,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>We investigated the use of mice transgenic for human leucocyte antigen (HLA) A*0201 antigen\u2010binding domains to test vaccines composed of defined HLA\u2003A*0201\u2010restricted cytotoxic T\u2010lymphocyte (CTL) epitopes of human papillomavirus (HPV) type 16 E7 oncoprotein. HPV is detected in &gt;90% of cervical carcinomas. HPV16 E7 oncoprotein transforms cells of the uterine cervix and functions as a tumour\u2010associated antigen to which immunotherapeutic strategies may be directed. We report that although the HLA\u2003A*0201 E7 epitope peptides function both to prime for E7 CTL responses, and to sensitize target cells for E7\u2010directed CTL killing in situations where antigen processing is not required, the epitopes are not processed out of either endogenously expressed or immunization\u2010introduced E7, by the mouse antigen\u2010processing and presentation machinery. Thus (1) CTL induced by HLA\u2003A*0201 peptide immunization killed E7 peptide\u2010pulsed target cells, but did not kill target cells expressing whole E7; (2) immunization with whole E7 protein did not elicit CTL directed to HLA\u2003A*0201\u2010restricted E7 CTL epitopes; (3) HLA\u2003A*0201\u2010restricted CTL epitopes expressed in the context of a DNA polytope vaccine did not activate E7\u2010specific T cells either in \u2018conventional\u2019 HLA\u2003A*0201 transgenic (A2.1K<jats:sup>b<\/jats:sup>) mice, or in HHD transgenic mice in which expression of endogenous H\u20102 class 1 is precluded; and (4) HLA\u2003A*0201 E7 peptide epitope immunization was incapable of preventing the growth of an HLA\u2003A*0201\u2010 and E7\u2010expressing tumour. There are generic implications for the universal applicability of HLA\u2010class 1 transgenic mice for studies of human CTL epitope presentation in murine models of human infectious disease where recognition of endogenously processed antigen is necessary. There are also specific implications for the use of HLA\u2003A2 transgenic mice for the development of E7\u2010based therapeutic vaccines for cervical cancer.<\/jats:p>","DOI":"10.1046\/j.1365-2567.2002.01442.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T02:31:31Z","timestamp":1047436291000},"page":"526-536","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Limitations of HLA\u2010transgenic mice in presentation of HLA\u2010restricted cytotoxic T\u2010cell epitopes from endogenously processed human papillomavirus type 16 E7 protein"],"prefix":"10.1111","volume":"106","author":[{"given":"Michael D.","family":"Street","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Doan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen 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