{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:59:16Z","timestamp":1791115156350,"version":"4.1.0"},"reference-count":14,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,6,7]]},"abstract":"<jats:p>In studying the subdominant status of two cysteine-containing influenza virus nuclear protein (NP) determinants (NP39\u201347 and NP218\u2013226) restricted by H-2Kd, we found that the antigenicity of synthetic peptides was enhanced 10\u2013100-fold by treatment with reducing agents, despite the fact that the affinity for Kd was not enhanced. Reducing agents also markedly enhanced the immunogenicity of cysteine-containing peptides, as measured by propagation of long-term T cell lines in vitro. Similar enhancing effects were obtained by substituting cysteine with alanine or serine in the synthetic peptides, demonstrating that sulfhydryl modification of cysteine is responsible for the impaired antigenicity and immunogenicity of NP39\u201347 and NP218\u2013226. We found similar effects for two widely studied, cysteine-containing peptides from lymphocytic choriomeningitis virus. The major modifications of cysteine-containing synthetic peptides are cysteinylation and dimerization occurring through cysteine residues. We demonstrate that both of these modifications occur in cells synthesizing a cytosolic NP218\u2013226 minigene product and, further, that T cells specific for cysteinylated NP218\u2013226 are induced by influenza virus infection in mice, demonstrating that this modification occurs in vivo. These findings demonstrate that posttranslational modifications affect the immunogenicity and antigenicity of cysteine-containing viral peptides and that this must be considered in studying the status of such peptides in immunodominance hierarchies.<\/jats:p>","DOI":"10.1084\/jem.189.11.1757","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"1757-1764","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":96,"title":["Modification of Cysteine Residues In Vitro and In Vivo Affects the Immunogenicity and Antigenicity of Major Histocompatibility Complex Class I\u2013restricted Viral Determinants"],"prefix":"10.1084","volume":"189","author":[{"given":"Weisan","family":"Chen","sequence":"first","affiliation":[{"name":"From the *Laboratory of \u2009Viral Diseases, National Institute of Allergy and Infectious Diseases, and the \u2021Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0440"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan W.","family":"Yewdell","sequence":"additional","affiliation":[{"name":"From the *Laboratory of \u2009Viral Diseases, National Institute of Allergy and Infectious Diseases, and the \u2021Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0440"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney L.","family":"Levine","sequence":"additional","affiliation":[{"name":"From the *Laboratory of \u2009Viral Diseases, National Institute of Allergy and Infectious Diseases, and the \u2021Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0440"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack 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