Abstract

CD8 expressing T cells play a critical role in eradicating intracellular parasites such as viruses. CD8 positive T cells recognize MHC class I molecules in a complex with peptides of 8 to 10 residues derived from viral proteins located in the cytosol. There is tremendous interest in the mechanism by which peptides are generated. Indirect evidence implicates proteasomes in the generation of antigenic peptides. Proteasomes are abundant macromolecular structures present in the cytosol and nucleus, and have multiple protease activities. They are thought to be responsible for energy dependent proteolysis in which ubiquitin plays a prominent role in targeting proteins for destruction. In this project we examine the contribution of proteasomes to the production of antigenic peptides as well as there importance to viral life cycles. Another goal is to identify sequences that enhance the immunogenicity of proteins by increasing their capacity to generate antigenic peptides. This project has also branched out into the study of the structure and function of individual viral proteins.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000658-14
Application #
7194089
Study Section
(LVD)
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2005
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

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
Yewdell, Jonathan W; Lev, Avital (2007) Self-reporting peptides illuminate the MHC groove. Nat Chem Biol 3:201-2
Pruszczyk, Piotr; Kostera-Pruszczyk, Anna; Shatunov, Alexey et al. (2007) Restrictive cardiomyopathy with atrioventricular conduction block resulting from a desmin mutation. Int J Cardiol 117:244-53
Tscharke, David C; Woo, Wai-Ping; Sakala, Isaac G et al. (2006) Poxvirus CD8+ T-cell determinants and cross-reactivity in BALB/c mice. J Virol 80:6318-23
Pasquetto, Valerie; Bui, Huynh-Hoa; Giannino, Rielle et al. (2005) HLA-A*0201, HLA-A*1101, and HLA-B*0702 transgenic mice recognize numerous poxvirus determinants from a wide variety of viral gene products. J Immunol 175:5504-15
Oseroff, Carla; Kos, Ferdynand; Bui, Huynh-Hoa et al. (2005) HLA class I-restricted responses to vaccinia recognize a broad array of proteins mainly involved in virulence and viral gene regulation. Proc Natl Acad Sci U S A 102:13980-5
Chanturiya, A N; Basanez, G; Schubert, U et al. (2004) PB1-F2, an influenza A virus-encoded proapoptotic mitochondrial protein, creates variably sized pores in planar lipid membranes. J Virol 78:6304-12
Eriksson, Maria; Brown, W Ted; Gordon, Leslie B et al. (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423:293-8
Yewdell, Jonathan W; Reits, Eric; Neefjes, Jacques (2003) Making sense of mass destruction: quantitating MHC class I antigen presentation. Nat Rev Immunol 3:952-61
Gibbs, James S; Malide, Daniela; Hornung, Felicita et al. (2003) The influenza A virus PB1-F2 protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function. J Virol 77:7214-24

Showing the most recent 10 out of 29 publications