Abstract

CD8 positive lymphocytes (TCD8+) play an important role in host immunity to viruses . Anti-viral TCD8+ recognize MHC class I molecules bound to peptides derived from a cytosolic pool of viral proteins. Concerning the delivery of antigenic peptides to MHC class I molecules, our studies have addressed two separate questions. First, since secreted viral proteins are co-translationally translocated into the endoplasmic reticulum (ER) and the ER has limited proteolytic machinery, the aim of this study is to determine how peptides are derived from secreted proteins. Second, there are two sources of antigenic peptides, native proteins and everything else. We have termed all the non-native sources, DRiPs, or defective ribosomal products. DRiPs consist of prematurely terminated polypeptides and misfolded polypeptides produced from translation products of bona fide mRNAs in the proper reading frame.
The second aim of this project is to examine the nature of the substrate from which antigenic peptides are derived and the their contribution to antigen presentation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000653-07
Application #
6099007
Study Section
Special Emphasis Panel (LVD)
Project Start
Project End
Budget Start
Budget End
Support Year
7
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

Hickman, Heather D; Mays, Jacqueline W; Gibbs, James et al. (2018) Influenza A Virus Negative Strand RNA Is Translated for CD8+ T Cell Immunosurveillance. J Immunol 201:1222-1228
Wei, Jiajie; Zanker, Damien; Di Carluccio, Anthony R et al. (2017) Varied Role of Ubiquitylation in Generating MHC Class I Peptide Ligands. J Immunol 198:3835-3845
Goldszmid, Romina S; Coppens, Isabelle; Lev, Avital et al. (2009) Host ER-parasitophorous vacuole interaction provides a route of entry for antigen cross-presentation in Toxoplasma gondii-infected dendritic cells. J Exp Med 206:399-410
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
Berglund, Peter; Finzi, Diana; Bennink, Jack R et al. (2007) Viral alteration of cellular translational machinery increases defective ribosomal products. J Virol 81:7220-9
Yewdell, Jonathan W; Nicchitta, Christopher V (2006) The DRiP hypothesis decennial: support, controversy, refinement and extension. Trends Immunol 27:368-73
Qian, Shu-Bing; Princiotta, Michael F; Bennink, Jack R et al. (2006) Characterization of rapidly degraded polypeptides in mammalian cells reveals a novel layer of nascent protein quality control. J Biol Chem 281:392-400
Qian, Shu-Bing; Reits, Eric; Neefjes, Jacques et al. (2006) Tight linkage between translation and MHC class I peptide ligand generation implies specialized antigen processing for defective ribosomal products. J Immunol 177:227-33
Yewdell, Jonathan W (2005) Immunoproteasomes: regulating the regulator. Proc Natl Acad Sci U S A 102:9089-90
Qian, Shu-Bing; Bennink, Jack R; Yewdell, Jonathan W (2005) Quantitating defective ribosome products. Methods Mol Biol 301:271-81

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