{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:29:54Z","timestamp":1787002194480,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,5,10]],"date-time":"2011-05-10T00:00:00Z","timestamp":1304985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["AI567122"],"award-info":[{"award-number":["AI567122"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI170251"],"award-info":[{"award-number":["AI170251"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP1095581"],"award-info":[{"award-number":["DP1095581"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2012,2]]},"abstract":"\n The emergence of the novel reassortant A(H1N1)\u20102009 influenza virus highlighted the threat to the global population posed by an influenza pandemic. Pre\u2010existing CD8\n +<\/jats:sup>\n T\u2010cell immunity targeting conserved epitopes provides immune protection against newly emerging strains of influenza virus, when minimal antibody immunity exists. However, the occurrence of mutations within T\u2010cell antigenic peptides that enable the virus to evade T\u2010cell recognition constitutes a substantial issue for virus control and vaccine design. Recent evidence suggests that it might be feasible to elicit CD8\n +<\/jats:sup>\n T\u2010cell memory pools to common virus mutants by pre\u2010emptive vaccination. However, there is a need for a greater understanding of CD8\n +<\/jats:sup>\n T\u2010cell immunity towards commonly emerging mutants. The present analysis focuses on novel and immunodominant, although of low pMHC\u2010I avidity, CD8\n +<\/jats:sup>\n T\u2010cell responses directed at the mutant influenza D\n b<\/jats:sup>\n NP\n 366<\/jats:sub>\n epitope, D\n b<\/jats:sup>\n NPM6A, following different routes of infection. We used a C57BL\/6J model of influenza to dissect the effectiveness of the natural intranasal (i.n.) versus intraperitoneal (i.p.) priming for generating functional CD8\n +<\/jats:sup>\n T cells towards the D\n b<\/jats:sup>\n NPM6A epitope. In contrast to comparable CD8\n +<\/jats:sup>\n T\u2010cell responses directed at the wild\u2010type epitopes, D\n b<\/jats:sup>\n NP\n 366<\/jats:sub>\n and D\n b<\/jats:sup>\n PA\n 224<\/jats:sub>\n , we found that the priming route greatly affected the numbers, cytokine profiles and TCR repertoire of the responding CD8\n +<\/jats:sup>\n T cells directed at the D\n b<\/jats:sup>\n NPM6A viral mutant. As the magnitude, polyfunctionality, and T\u2010cell repertoire diversity are potential determinants of the protective efficacy of CD8\n +<\/jats:sup>\n T\u2010cell responses, our data have implications for the development of vaccines to combat virus mutants.\n <\/jats:p>","DOI":"10.1038\/icb.2011.36","type":"journal-article","created":{"date-parts":[[2011,5,10]],"date-time":"2011-05-10T05:37:44Z","timestamp":1305005864000},"page":"216-223","source":"Crossref","is-referenced-by-count":9,"title":["Consequences of suboptimal priming are apparent for low\u2010avidity T\u2010cell responses"],"prefix":"10.1111","volume":"90","author":[{"given":"Vanessa","family":"Venturi","sequence":"first","affiliation":[{"name":"Computational Biology Group, Centre for Vascular Research, University of New South Wales Kensington New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miles P","family":"Davenport","sequence":"additional","affiliation":[{"name":"Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales Kensington New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha G","family":"Swan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C","family":"Doherty","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne Parkville Victoria Australia"},{"name":"Department of Immunology, St Jude Children's Research Hospital Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Kedzierska","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,5,10]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2011.01.007"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.5.2567-2572.2002"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.2453"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.10.5216-5222.2004"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82120-0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/346629a0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.4.1297"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069660"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.21.11507-11516.2003"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.10.010"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.9.5721-5731.2005"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21049"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040638"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00386.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1175"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810274105"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1007270107"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001039"},{"key":"e_1_2_8_19_1","first-page":"643","article-title":"Future 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