{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T03:43:45Z","timestamp":1776311025997,"version":"3.50.1"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1994,4,1]]},"abstract":"<jats:p>Epstein-Barr virus (EBV) is a B lymphotropic herpesvirus of humans that elicits strong HLA class I-restricted cytotoxic T lymphocyte (CTL) responses. An influence of such responses on virus evolution was first suggested by our finding that EBV isolates from the highly HLA A11-positive Papua New Guinea (PNG) population carried a lys-thr mutation at residue 424 of the nuclear antigen EBV-encoded nuclear antigen (EBNA4) that destroyed the immunodominant target epitope for A11-restricted CTL recognition. Here we turn to a much larger population, Southern Chinese, where the A11 allele is again present in over 50% of the individuals. Each of 23 EBV isolates analyzed from this population were also mutated in the EBNA4 416-424 epitope, the mutations selectively involving one of the two anchor residues in positions 2 (417 val-leu) or 9 (424 lys-asp, -arg or -thr) that are critical for A11-peptide interaction. The majority of the Chinese isolates and all 10 PNG isolates also carried mutations affecting positions 1 and 2 of the next most immunodominant A11-restricted epitope, EBNA4 residues 399-408. These changes clearly affected antigenicity since A11-positive lymphoblastoid cell lines (LCLs) carrying these mutant EBV strains were not recognized by A11-restricted CTLs raised against the prototype B95.8 virus. Furthermore, Chinese donors naturally infected with these mutant viruses did not mount detectable A11-restricted CTL responses on in vitro stimulation with autologous LCL cells carrying either the B95.8 or their endogenous EBV strain. In two different highly A11-positive populations, therefore, immune pressure appears to have selected for resident EBV strains lacking immunodominant A11-restricted CTL epitopes.<\/jats:p>","DOI":"10.1084\/jem.179.4.1297","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"1297-1305","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":122,"title":["T cell responses and virus evolution: loss of HLA A11-restricted CTL epitopes in Epstein-Barr virus isolates from highly A11-positive populations by selective mutation of anchor residues."],"prefix":"10.1084","volume":"179","author":[{"given":"P O","family":"de Campos-Lima","sequence":"first","affiliation":[{"name":"Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V","family":"Levitsky","sequence":"additional","affiliation":[{"name":"Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Brooks","sequence":"additional","affiliation":[{"name":"Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S P","family":"Lee","sequence":"additional","affiliation":[{"name":"Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L F","family":"Hu","sequence":"additional","affiliation":[{"name":"Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A B","family":"Rickinson","sequence":"additional","affiliation":[{"name":"Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M G","family":"Masucci","sequence":"additional","affiliation":[{"name":"Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1994,4,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/179\/4\/1297\/1675680\/1297.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/179\/4\/1297\/1675680\/1297.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T05:59:36Z","timestamp":1690264776000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/179\/4\/1297\/25036\/T-cell-responses-and-virus-evolution-loss-of-HLA"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,4,1]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1994,4,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.179.4.1297","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,4,1]]}}}