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However, the full range of parameters that determine immunodominance and the underlying mechanisms remain unknown. In this study, we show across a range of vaccinia virus strains, including the current clonal smallpox vaccine, that the ability of a strain to spread systemically correlated with reduced immunodominance. Reduction in immunodominance was observed both in the lymphoid system and at the primary site of infection. Mechanistically, reduced immunodominance was associated with more robust priming and especially priming in the spleen. Finally, we show this is not just a property of vaccine and laboratory strains of virus, because an association between virulence and immunodominance was also observed in isolates from an outbreak of zoonotic vaccinia virus that occurred in Brazil.<\/jats:p>","DOI":"10.4049\/jimmunol.1402508","type":"journal-article","created":{"date-parts":[[2015,7,21]],"date-time":"2015-07-21T01:44:34Z","timestamp":1437443074000},"page":"2263-2272","source":"Crossref","is-referenced-by-count":12,"title":["Extent of Systemic Spread Determines CD8+ T Cell Immunodominance for Laboratory Strains, Smallpox Vaccines, and Zoonotic Isolates of Vaccinia Virus"],"prefix":"10.1093","volume":"195","author":[{"given":"Inge E A","family":"Flesch","sequence":"first","affiliation":[{"name":"Research School of Biology, Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha A","family":"Hollett","sequence":"additional","affiliation":[{"name":"Research School of Biology, Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yik Chun","family":"Wong","sequence":"additional","affiliation":[{"name":"Research School of Biology, Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1rbara Resende","family":"Quinan","sequence":"additional","affiliation":[{"name":"Research School of Biology, Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]},{"name":"Laborat\u00f3rio de Virologia B\u00e1sica e Aplicada, Departamento de Microbiologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais 31270-901 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debbie","family":"Howard","sequence":"additional","affiliation":[{"name":"John Curtin School of Medical Research, Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fl\u00e1vio G","family":"da Fonseca","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Virologia B\u00e1sica e Aplicada, Departamento de Microbiologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais 31270-901 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C","family":"Tscharke","sequence":"additional","affiliation":[{"name":"Research School of Biology, Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]},{"name":"John Curtin School of Medical Research, Australian National University , Canberra, Australian Capital Territory 2601 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,9,1]]},"reference":[{"key":"2025030704070287900_r1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/329512a0","article-title":"The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens","volume":"329","author":"Bjorkman","year":"1987","journal-title":"Nature"},{"key":"2025030704070287900_r2","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1146\/annurev.immunol.23.021704.115702","article-title":"Understanding presentation of viral antigens to CD8+ T cells in vivo: the key to rational vaccine design","volume":"23","author":"Yewdell","year":"2005","journal-title":"Annu. 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