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Endogenous antigen\u2010processing function is restored in BL lines that have undergone Epstein\u2010Barr virus (EBV)\u2010induced drift in culture to the group III phenotype typically displayed by EBV\u2010transformed lymphoblastoid cell lines (LCL) of normal B cell origin. We compared group I versus group III cells for their expression of proteasome components, transporter proteins and HLA\u2010class I antigens, all of which are thought to be involved in the endogenous antigen processing pathway. By Western blot analysis, there were not consistent differences in the low molecular mass protein subunits of proteasomes (lmp)\u20102, lmp\u20107 and \u03b4, although the mb\u20101 proteasome subunit was regularly present at higher levels in group I BL lines relative to group III lines or LCL. By contrast there were marked differences in the expression of peptide transporter\u2010associated proteins (Tap), with down\u2010regulation of Tap\u20101 and Tap\u20102 in 8\/8 and 7\/8 group I BL lines, respectively. Surface levels of HLA class I antigens were also consistently lower in group I cells; this was not associated with an intracellular accumulation of free HLA heavy chains, such as is seen in the Tap\u2010deficient T2 processing\u2010mutant line, but instead reflected a reduced rate of HLA class I synthesis in group I cells. Analysis of EBV gene transfectants of the B lymphoma lines BJAB and BL41 showed that the virus\u2010encoded latent membrane protein\u20101 (LMP1), which is one of several EBV antigens expressed in group III but not in group I cells, was uniquely able to up\u2010regulate expression both of the Tap proteins and HLA class I. Furthermore, this was accompanied by a restoration of antigen\u2010processing function as measured by the ability of these cells to present an endogenously expressed viral antigen to CTL. These effects of LMP1 were similar to those induced in the same cell lines by interferon\u2010\u03b3 treatment. The results implicate both Tap and HLA class I expression as factors limiting the antigen\u2010processing function of BL cells, and suggest that the accessibility of other EBV\u2010associated malignancies to CTL surveillance may be critically dependent upon their LMP1 status.<\/jats:p>","DOI":"10.1002\/eji.1830250536","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T01:07:04Z","timestamp":1172797624000},"page":"1374-1384","source":"Crossref","is-referenced-by-count":161,"title":["Restoration of endogenous antigen processing in Burkitt's lymphoma cells by Epstein\u2010Barr virus latent membrane protein\u20101: coordinate up\u2010regulation of peptide transporters and HLA\u2010class I antigen expression"],"prefix":"10.1002","volume":"25","author":[{"given":"Martin","family":"Rowe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Khanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Argaet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Powis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Belich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Groom\u2010Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott R.","family":"Burrows","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Trowsdale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis J.","family":"Moss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan B.","family":"Rickinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,11,17]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.3.779"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/smvy.1994.1031"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(81)90115-X"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(82)92479-5"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910220604"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/297413a0"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/317629a0"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/312449a0"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1987.tb02568.x"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-71-7-1481"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/smvy.1994.1043"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198910193211604"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.6.1811"},{"key":"e_1_2_1_15_2","doi-asserted-by":"crossref","first-page":"5154","DOI":"10.4049\/jimmunol.150.11.5154","volume":"150","author":"Khanna R.","year":"1993","journal-title":"J. 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