Protective Efficacy of Serially Up-Ranked Subdominant CD8+ T Cell Epitopes against Virus Challenges

PLoS Pathogens

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