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Discovering protective T-cell responses by interrogating naturally processed antigenic determinants
Departmental Papers (Biology)
  • Pavlo Gilchuk, Vanderbilt University
  • Stephanie B Conant, Vanderbilt University
  • Hill Timothy, Vanderbilt University
  • Jennifer J Gray, Vanderbilt University
  • Xinann Niu, Vanderbilt University
  • Mu Zheng, Vanderbilt University
  • John Erickson, Vanderbilt University
  • Kelli Boyd, Vanderbilt University
  • Jennifer McAfee, Vanderbilt University
  • Carla Oseroff, La Jolla Institute of Allergy and Immunology
  • Sine Hadrup
  • Jack Bennink
  • William Hildebrand
  • Kathryn Edwards, Vanderbilt University
  • James E Crowe, Vanderbilt University
  • John Williams, Vanderbilt University
  • Soren Buus
  • Alessandro Sette, La Jolla Institute of Allergy and Immunology
  • Ton N Schumacher
  • Andrew J Link, Vanderbilt University
  • Sebastian Joyce, Vanderbilt University
  • Charles Spencer, University of Texas El Paso
Publication Date
Document Type
CD8+ T cells (TCD8) confer protective immunity against many infectious diseases, suggesting that microbial TCD8 determinants are promising vaccine targets. Nevertheless, current T cell antigen identification approaches do not discern which epitopes drive protective immunity during active infection - information that is critical for the rational design of TCD8-targeted vaccines. We employed a proteomics-based approach for large-scale discovery of naturally processed determinants derived from a complex pathogen, vaccinia virus (VACV), that are presented by the most frequent representatives of four major HLA class I supertypes. Immunologic characterization revealed that many previously unidentified VACV determinants were recognized by smallpox-vaccinated human peripheral blood cells in a variegated manner. Many such determinants were recognized by HLA class I-transgenic mouse immune TCD8 too and elicited protective TCD8 immunity against lethal intranasal VACV infection. Notably, efficient processing and stable presentation of immune determinants as well as the availability of naive TCD8 precursors were sufficient to drive a multifunctional, protective TCD8 response. Our approach uses fundamental insights into T cell epitope processing and presentation to define targets of protective TCD8 immunity within human pathogens that have complex proteomes, suggesting that this approach has general applicability in vaccine sciences.
Citation Information
Pavlo Gilchuk, Stephanie B Conant, Hill Timothy, Jennifer J Gray, et al.. "Discovering protective T-cell responses by interrogating naturally processed antigenic determinants" (2013)
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