PLoS Pathogens | |
Protective Efficacy of Serially Up-Ranked Subdominant CD8+ T Cell Epitopes against Virus Challenges | |
Peter Liljeström1  Eung-Jun Im2  Tomáš Hanke2  Anne Bridgeman2  Jessie P. Hong2  Sven Létourneau2  Yaowaluck Roshorm2  Andrew J. McMichael2  David J. Volsky3  Mary Jane Potash3  | |
[1] Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden;MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Oxford, United Kingdom;Molecular Virology Division, St. Luke's Roosevelt Hospital Center, Columbia University Medical Center, New York, New York, United States of America | |
关键词: T cells; Cytotoxic T cells; Immune response; Antigens; HIV-1; Vaccines; Vaccination; immunization; Enzyme-linked immunoassays; | |
DOI : 10.1371/journal.ppat.1002041 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
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.
【 授权许可】
CC BY
【 预 览 】
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