{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:15:31Z","timestamp":1791404131067,"version":"4.3.3"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2008,11,1]],"date-time":"2008-11-01T00:00:00Z","timestamp":1225497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hepatitis C virus (HCV) infection frequently persists despite eliciting substantial virus-specific immune responses. Thus, HCV infection provides a setting in which to investigate mechanisms of immune escape that allow for viral persistence. Viral amino acid substitutions resulting in decreased MHC binding or impaired Ag processing of T cell epitopes reduce Ag density on the cell surface, permitting evasion of T cell responses in chronic viral infection. Substitutions in viral epitopes that alter TCR contact residues frequently result in escape, but via unclear mechanisms because such substitutions do not reduce surface presentation of peptide-MHC complexes and would be expected to prime T cells with new specificities. We demonstrate that a known in vivo HCV mutation involving a TCR contact residue significantly diminishes T cell recognition and, in contrast to the original sequence, fails to effectively prime naive T cells. This mutant epitope thus escapes de novo immune recognition because there are few highly specific cognate TCR among the primary human T cell repertoire. This example is the first on viral immune escape via exploitation of a \u201chole\u201d in the T cell repertoire, and may represent an important general mechanism of viral persistence.<\/jats:p>","DOI":"10.4049\/jimmunol.181.9.6435","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:03:28Z","timestamp":1397862208000},"page":"6435-6446","source":"Crossref","is-referenced-by-count":63,"title":["Hepatitis C Virus Immune Escape via Exploitation of a Hole in the T Cell Repertoire"],"prefix":"10.1093","volume":"181","author":[{"given":"Matthias","family":"W\u00f6lfl","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alleluiah","family":"Rutebemberwa","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Mosbruger","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Southwest Hospital, Third Military Medical University , Chongqing,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-mei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Netski","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart C.","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Department of Oncology, Johns Hopkins Medical Institutions , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drew","family":"Pardoll","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Department of Oncology, Johns Hopkins Medical Institutions , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sidney","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Allergy and Immunology , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Sette","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Allergy and Immunology , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Allen","sequence":"additional","affiliation":[{"name":"Partners AIDS Research Center , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kuntzen","sequence":"additional","affiliation":[{"name":"Partners AIDS Research Center , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Kavanagh","sequence":"additional","affiliation":[{"name":"Partners AIDS Research Center , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Kuball","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip D.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Department of Oncology, Johns Hopkins Medical Institutions , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,11,1]]},"reference":[{"key":"2025032700362114000_R1","first-page":"S70","article-title":"Social and environmental risk factors in the emergence of infectious diseases","volume-title":"Nat. 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