Loading…

Protective efficacy of serially up-ranked subdominant CD8+ T cell epitopes against virus challenges

Immunodominance in T cell responses to complex antigens like viruses is still incompletely understood. Some data indicate that the dominant responses to viruses are not necessarily the most protective, while other data imply that dominant responses are the most important. The issue is of considerabl...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2011-05, Vol.7 (5), p.e1002041-e1002041
Main Authors: Im, Eung-Jun, Hong, Jessie P, Roshorm, Yaowaluck, Bridgeman, Anne, Létourneau, Sven, Liljeström, Peter, Potash, Mary Jane, Volsky, David J, McMichael, Andrew J, Hanke, Tomáš
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Immunodominance in T cell responses to complex antigens like viruses is still incompletely understood. Some data indicate that the dominant responses to viruses are not necessarily the most protective, while other data imply that dominant responses are the most important. The issue is of considerable importance to the rational design of vaccines, particularly against variable escaping viruses like human immunodeficiency virus type 1 and hepatitis C virus. Here, we showed that sequential inactivation of dominant epitopes up-ranks the remaining subdominant determinants. Importantly, we demonstrated that subdominant epitopes can induce robust responses and protect against whole viruses if they are allowed at least once in the vaccination regimen to locally or temporally dominate T cell induction. Therefore, refocusing T cell immune responses away from highly variable determinants recognized during natural virus infection towards subdominant, but conserved regions is possible and merits evaluation in humans.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1002041