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In the few exceptional cases where TAP\u2010independent presentation of an endogenously expressed protein has been observed, the epitope\u2010containing domain of the protein either has naturally accessed or has been directed into the ER lumen where it is thought to become susceptible to ER proteases. Here, we describe a novel example of TAP\u2010independent processing involving the Epstein\u2010Barr virus (EBV) latent membrane protein LMP2, a multiple membrane\u2010spanning protein with minimal projection into the ER. Expression of LMP2 in the TAP<jats:sup>\u2212<\/jats:sup> T2 cell line, whether from the resident EBV genome or from a recombinant vaccinia virus vector vacc\u2010LMP2, rendered the cells sensitive to recognition by CTL clones specific for two HLA\u2010A2.1\u2010restricted peptide epitopes, LMP2 329\u2013337 or 426\u2013434. Vacc\u2010LMP2\u2010mediated sensitization to lysis required expression of the antigen <jats:italic>de novo<\/jats:italic> in T2 cells and was blocked by brefeldin A. In the same experiments, two other EBV\u2010specific CTL epitopes, one derived from LMP2 but restricted through a different HLA allele (A11), the other restricted through A2.1 but derived from a different viral protein (BMLF1), did not display TAP\u2010independent processing. The results are discussed in relation to the unusual topology of LMP2 in the membrane and the position of the epitope peptides within that structure.<\/jats:p>","DOI":"10.1002\/eji.1830260831","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T02:39:17Z","timestamp":1172803157000},"page":"1875-1883","source":"Crossref","is-referenced-by-count":46,"title":["Transporter (TAP)\u2010independent processing of a multiple membrane\u2010spanning protein, the Epstein\u2010Barr virus latent membrane protein 2"],"prefix":"10.1002","volume":"26","author":[{"given":"Steven P.","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy A.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil W.","family":"Blake","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan B.","family":"Rickinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,17]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90336-0"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.64.070195.002335"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8342042"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)80058-M"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/348248a0"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/345449a0"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/360171a0"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/360174a0"},{"key":"e_1_2_1_10_2","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.4049\/jimmunol.152.3.1163","volume":"152","author":"Yewdell J.","year":"1994","journal-title":"J. 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