NDLI: Immunoproteasomes Shape Immunodominance Hierarchies of Antiviral Cd8+ T Cells at the Levels of T Cell Repertoire and Presentation of Viral Antigens

Content Provider	PubMed Central
Author	Chen, Weisan Norbury, Christopher C. Cho, Yunjung Yewdell, Jonathan W. Bennink, Jack R.
Copyright Year	2001
Abstract	Vertebrates express three cytokine-inducible proteasome subunits that are incorporated in the place of their constitutively synthesized counterparts. There is increasing evidence that the set of peptides generated by proteasomes containing these subunits (immunoproteasomes) differs from that produced by standard proteasomes. In this study, we use mice lacking one of the immunoproteasome subunits (LMP2) to show that immunoproteasomes play an important role in establishing the immunodominance hierarchy of CD8+ T cells (TCD8+) responding to seven defined determinants in influenza virus. In LMP2−/− mice, responses to the two most dominant determinants drop precipitously, whereas responses to two subdominant determinants are greatly enhanced. Adoptive transfer experiments with naive normal and transgenic TCD8+ reveal that the reduced immunogenicity of one determinant (PA224–233) can be attributed to decreased generation by antigen presenting cells (APCs), whereas the other determinant (NP366–374) is less immunogenic due to alterations in the TCD8+ repertoire, and not, as reported previously, to the decreased capacity of LMP2−/− APCs to generate the determinant. The enhanced response to one of the subdominant determinants (PB1F262–70) correlates with increased generation by LMP2 − /− virus–infected cells. These findings indicate that in addition to their effects on the presentation of foreign antigens, immunoproteasomes influence TCD8+ responses by modifying the repertoire of responding TCD8+.
Starting Page	1319
File Format	PDF
ISSN	15409538
e-ISSN	15409538
Journal	The Journal of Experimental Medicine
Issue Number	11
Volume Number	193
Language	English
Publisher	The Rockefeller University Press
Publisher Date	2001-06-04
Access Restriction	Open
Rights Holder	The Rockefeller University Press
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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