Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms

Scott Hansen, Jonah Sacha, Colette M. Hughes, Julia C. Ford, Benjamin Burwitz, Isabel Scholz, Roxanne M. Gilbride, Matthew S. Lewis, Awbrey N. Gilliam, Abigail B. Ventura, Daniel Malouli, Guangwu Xu, Rebecca Richards, Nathan Whizin, Jason S. Reed, Katherine B. Hammond, Miranda Fischer, John M. Turner, Alfred W. Legasse, Michael AxthelmPaul T. Edlefsen, Jay Nelson, Jeffrey D. Lifson, Klaus Frueh, Louis Picker

Research output: Contribution to journalArticle

251 Citations (Scopus)

Abstract

CD8+ T cell responses focus on a small fraction of pathogen- or vaccine-encoded peptides, and for some pathogens, these restricted recognition hierarchies limit the effectiveness of antipathogen immunity. We found that simian immunodeficiency virus (SIV) protein-expressing rhesus cytomegalovirus (RhCMV) vectors elicit SIV-specific CD8+ T cells that recognize unusual, diverse, and highly promiscuous epitopes, including dominant responses to epitopes restricted by class II major histocompatibility complex (MHC) molecules. Induction of canonical SIV epitope-specific CD8+ T cell responses is suppressed by the RhCMV-encoded Rh189 gene (corresponding to human CMV US11), and the promiscuous MHC class I- and class II-restricted CD8 + T cell responses occur only in the absence of the Rh157.5, Rh157.4, and Rh157.6 (human CMV UL128, UL130, and UL131) genes. Thus, CMV vectors can be genetically programmed to achieve distinct patterns of CD8+ T cell epitope recognition.

Original languageEnglish (US)
Article number1237874
JournalScience
Volume340
Issue number6135
DOIs
StatePublished - 2013

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T-Lymphocyte Epitopes
Cytomegalovirus
Simian Immunodeficiency Virus
T-Lymphocytes
Epitopes
Major Histocompatibility Complex
Subunit Vaccines
Genes
Immunity
Proteins

ASJC Scopus subject areas

  • General
  • Medicine(all)

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Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. / Hansen, Scott; Sacha, Jonah; Hughes, Colette M.; Ford, Julia C.; Burwitz, Benjamin; Scholz, Isabel; Gilbride, Roxanne M.; Lewis, Matthew S.; Gilliam, Awbrey N.; Ventura, Abigail B.; Malouli, Daniel; Xu, Guangwu; Richards, Rebecca; Whizin, Nathan; Reed, Jason S.; Hammond, Katherine B.; Fischer, Miranda; Turner, John M.; Legasse, Alfred W.; Axthelm, Michael; Edlefsen, Paul T.; Nelson, Jay; Lifson, Jeffrey D.; Frueh, Klaus; Picker, Louis.

In: Science, Vol. 340, No. 6135, 1237874, 2013.

Research output: Contribution to journalArticle

Hansen, S, Sacha, J, Hughes, CM, Ford, JC, Burwitz, B, Scholz, I, Gilbride, RM, Lewis, MS, Gilliam, AN, Ventura, AB, Malouli, D, Xu, G, Richards, R, Whizin, N, Reed, JS, Hammond, KB, Fischer, M, Turner, JM, Legasse, AW, Axthelm, M, Edlefsen, PT, Nelson, J, Lifson, JD, Frueh, K & Picker, L 2013, 'Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms', Science, vol. 340, no. 6135, 1237874. https://doi.org/10.1126/science.1237874
Hansen, Scott ; Sacha, Jonah ; Hughes, Colette M. ; Ford, Julia C. ; Burwitz, Benjamin ; Scholz, Isabel ; Gilbride, Roxanne M. ; Lewis, Matthew S. ; Gilliam, Awbrey N. ; Ventura, Abigail B. ; Malouli, Daniel ; Xu, Guangwu ; Richards, Rebecca ; Whizin, Nathan ; Reed, Jason S. ; Hammond, Katherine B. ; Fischer, Miranda ; Turner, John M. ; Legasse, Alfred W. ; Axthelm, Michael ; Edlefsen, Paul T. ; Nelson, Jay ; Lifson, Jeffrey D. ; Frueh, Klaus ; Picker, Louis. / Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. In: Science. 2013 ; Vol. 340, No. 6135.
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AU - Xu, Guangwu

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AU - Reed, Jason S.

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AU - Fischer, Miranda

AU - Turner, John M.

AU - Legasse, Alfred W.

AU - Axthelm, Michael

AU - Edlefsen, Paul T.

AU - Nelson, Jay

AU - Lifson, Jeffrey D.

AU - Frueh, Klaus

AU - Picker, Louis

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