Abstract

CD8 + T cells (TCD8+) play a crucial role in eradicating viral infections. Despite this, little attention has been paid to the ability of vaccines to induce TCD8+ memory. For viruses in which traditional vaccine approaches have not been successful, it is hoped that induction of TCD8+ memory will enhance immunity. To induce optimal TCD8+ responses to vaccines it is necessary to understand how primary TCD8+ cells are stimulated. The goal of this project is to answer the following questions; 1. Following a virus infection in what anatomical location are primary TCD8+ cells stimulated (local sites of infection, lymph nodes, spleen)? 2. What type of cell presents antigen to primary TCD8+ cells? 3. Is the antigen presenting cell infected, or does it present viral proteins obtained from infected cells? 4. How does these answers to questions 1-3 vary between different antigens encoded by the same virus and the same antigen encoded by different viruses?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000814-02
Application #
6099128
Study Section
Special Emphasis Panel (LVD)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Haeryfar, S M Mansour; Hickman, Heather D; Irvine, Kari R et al. (2008) Terminal deoxynucleotidyl transferase establishes and broadens antiviral CD8+ T cell immunodominance hierarchies. J Immunol 181:649-59
Lev, Avital; Takeda, Kazuyo; Zanker, Damien et al. (2008) The exception that reinforces the rule: crosspriming by cytosolic peptides that escape degradation. Immunity 28:787-98
Hensley, Scott E; Amalfitano, Andrea (2007) Toll-like receptors impact on safety and efficacy of gene transfer vectors. Mol Ther 15:1417-22
Hickman-Miller, Heather D; Yewdell, Jonathan W (2006) Youth has its privileges: maturation inhibits DC cross-priming. Nat Immunol 7:125-6
Thilo, Claudia; Berglund, Peter; Applequist, Steven E et al. (2006) Dissection of the interaction of the human cytomegalovirus-derived US2 protein with major histocompatibility complex class I molecules: prominent role of a single arginine residue in human leukocyte antigen-A2. J Biol Chem 281:8950-7
Yewdell, Jonathan W (2006) Confronting complexity: real-world immunodominance in antiviral CD8+ T cell responses. Immunity 25:533-43
Tscharke, David C; Karupiah, Gunasegaran; Zhou, Jie et al. (2005) Identification of poxvirus CD8+ T cell determinants to enable rational design and characterization of smallpox vaccines. J Exp Med 201:95-104
Truckenmiller, Mary E; Princiotta, Michael F; Norbury, Christopher C et al. (2005) Corticosterone impairs MHC class I antigen presentation by dendritic cells via reduction of peptide generation. J Neuroimmunol 160:48-60
Prlic, Martin; Gibbs, James; Jameson, Stephen C (2005) Characteristics of NK cell migration early after vaccinia infection. J Immunol 175:2152-7
Chen, Weisan; Masterman, Kelly-Anne; Basta, Sameh et al. (2004) Cross-priming of CD8+ T cells by viral and tumor antigens is a robust phenomenon. Eur J Immunol 34:194-9

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