Delivery of Antigens to the MHC Class I Processing Pathway

Yewdell, J W.

Abstract

CD8 positive lymphocytes (T/CD8+) play an important role in host immunity to viruses . Anti-viral T/CD8+ recognize MHC class I molecules bound to peptides derived from a cytosolic pool of viral proteins. One of the curious features of T/CD8+ responses to viral infections is that it typically focuses on a highly limited set of peptides. This phenomenon, termed immunodominance, is crucial to understand if we are to develop vaccines that optimally elicit T/CD8+ responses. In this project we are investigating the various factors that contribute to immunodominance, including antigen processing, T cell regulation, and T cell receptor repertoire.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000653-06
• Application #: 6160682
• Study Section: Special Emphasis Panel (LVD)
• Support Year: 6
• Fiscal Year: 1997

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

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