Heat-aggregated noninfectious influenza virus induces a more balanced CD8+-T-lymphocyte immunodominance hierarchy than infectious virus

Yunjung Cho, Sameh Basta, Weisan Chen, Jack R. Bennink, Jonathan W. Yewdell

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

CD8+-T-cell (TCD8+) responses to infectious viruses are characterized by an immunodominance hierarchy in which the majority of TCD8+ respond to one or a few immunodominant determinants, with a minority of TCD8+ responding to a number of subdominant determinants. It is now well established that exogenous antigens are capable of inducing TCD8+ to such immunodominant determinants, but the diversity of the response and the nature of the immunodominance hierarchy have not been examined. We addressed this issue by characterizing TCD8+ responses to influenza virus preparations rendered inert by incubation for 10 min at 100°C, as first reported by Speidel et al. (Eur. J. Immunol. 27:2391-2399, 1997). Extending these findings, we show that the primary TCD8+ response to boiled virus can be sufficiently robust to be detected ex vivo by intracellular cytokine staining and that the response encompasses many of the peptides recognized by TCD8+ induced by infectious virus. Importantly, the immunodominance hierarchy elicited was leveled, and we were unable to detect TCD8+ that were specific for boiled virus. We used peritoneal exudate cells as antigen-presenting cells in vitro, and a number of observations indicated that boiled virus is processed via a phagocytic route that is likely to be endosomal in nature. These findings suggest that the repertoires of immunogenic peptides generated by endosomes and cytosolic processes overlap to a surprising degree. Furthermore, they demonstrate that the form of antigen administered can influence immunodominance hierarchies and that exogenous-antigen vaccines can induce broad and balanced TCD8+ responses.

Original languageEnglish
Pages (from-to)4679-4684
Number of pages6
JournalJournal of Virology
Volume77
Issue number8
DOIs
Publication statusPublished - 2003 Apr 1

Fingerprint

Orthomyxoviridae
T-lymphocytes
Hot Temperature
Viruses
T-Lymphocytes
heat
viruses
Immunodominant Epitopes
antigens
Antigens
peptides
Peptides
endosomes
antigen-presenting cells
Endosomes
Exudates and Transudates
Antigen-Presenting Cells
cytokines
Vaccines
Staining and Labeling

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Heat-aggregated noninfectious influenza virus induces a more balanced CD8+-T-lymphocyte immunodominance hierarchy than infectious virus. / Cho, Yunjung; Basta, Sameh; Chen, Weisan; Bennink, Jack R.; Yewdell, Jonathan W.

In: Journal of Virology, Vol. 77, No. 8, 01.04.2003, p. 4679-4684.

Research output: Contribution to journalArticle

Cho, Yunjung ; Basta, Sameh ; Chen, Weisan ; Bennink, Jack R. ; Yewdell, Jonathan W. / Heat-aggregated noninfectious influenza virus induces a more balanced CD8+-T-lymphocyte immunodominance hierarchy than infectious virus. In: Journal of Virology. 2003 ; Vol. 77, No. 8. pp. 4679-4684.
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