The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Singh, R. A. K.
Right arrow Articles by Barry, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Singh, R. A. K.
Right arrow Articles by Barry, M. A.
The Journal of Immunology, 2002, 169: 6779-6786.
Copyright © 2002 by The American Association of Immunologists

The Role of T Cell Antagonism and Original Antigenic Sin in Genetic Immunization1

Rana A. K. Singh*, John R. Rodgers{ddagger} and Michael A. Barry2,*,{dagger},{ddagger},§

* Center for Cell and Gene Therapy, Departments of {dagger} Molecular and Human Genetics and {ddagger} Immunology, Baylor College of Medicine, Houston, TX 77030; and § Department of Bioengineering, Rice University, Houston, TX 77005

To counter highly mutable pathogens like HIV-1, a number of vaccines are being developed to deliver multiple mutant forms of viral Ags to provoke multivalent antiviral CTLs. However, it is uncertain whether such multiple mutant epitope vaccines will generate the diverse CTL responses desired or will instead create immune interference. To characterize the role of immune interference by mutant epitopes in this process, we have tested a "worst case" scenario in which the immunodominant epitope of OVA (SIINFEKL) and its in vitro TCR antagonist (SIINFEDL) have been used to genetically immunize C57BL/6 mice. We demonstrate here that sequential delivery of these mutant epitopes provokes original antigenic sin in CD8 T cells as demonstrated by attenuation of CTLs, intracellular IFN-{gamma} production, and MHC I peptide-tetramer staining. By contrast, simultaneous exposure of the immune system to this agonist/antagonist pair not only fails to generate T cell antagonism in vivo, but also avoids original antigenic sin. These observations suggest that simultaneous immunization with vaccines containing mutant epitopes, even T cell antagonists, can indeed generate a diverse array of T cell responses and that at least some immune interference can be avoided by delivering mutant Ags to the immune system simultaneously.




This article has been cited by other articles:


Home page
 J. Virol.Home page
J. Liu, B. A. Ewald, D. M. Lynch, A. Nanda, S. M. Sumida, and D. H. Barouch
Modulation of DNA Vaccine-Elicited CD8+ T-Lymphocyte Epitope Immunodominance Hierarchies
J. Virol., December 15, 2006; 80(24): 11991 - 11997.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
G. M. A. Gillespie, G. Stewart-Jones, J. Rengasamy, T. Beattie, Job. J. Bwayo, F. A. Plummer, R. Kaul, A. J. McMichael, P. Easterbrook, T. Dong, et al.
Strong TCR Conservation and Altered T Cell Cross-Reactivity Characterize a B*57-Restricted Immune Response in HIV-1 Infection
J. Immunol., September 15, 2006; 177(6): 3893 - 3902.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
X. S. Liu, J. Dyer, G. R. Leggatt, G. J. P. Fernando, J. Zhong, R. Thomas, and I. H. Frazer
Overcoming Original Antigenic Sin to Generate New CD8 T Cell IFN-{gamma} Responses in an Antigen-Experienced Host.
J. Immunol., September 1, 2006; 177(5): 2873 - 2879.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
L. Dorrell, H. Yang, B. Ondondo, T. Dong, K. di Gleria, A. Suttill, C. Conlon, D. Brown, P. Williams, P. Bowness, et al.
Expansion and Diversification of Virus-Specific T Cells following Immunization of Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Individuals with a Recombinant Modified Vaccinia Virus Ankara/HIV-1 Gag Vaccine.
J. Virol., May 1, 2006; 80(10): 4705 - 4716.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
T. M. Allen, X. G. Yu, E. T. Kalife, L. L. Reyor, M. Lichterfeld, M. John, M. Cheng, R. L. Allgaier, S. Mui, N. Frahm, et al.
De Novo Generation of Escape Variant-Specific CD8+ T-Cell Responses following Cytotoxic T-Lymphocyte Escape in Chronic Human Immunodeficiency Virus Type 1 Infection
J. Virol., October 15, 2005; 79(20): 12952 - 12960.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
K. Sugimoto, D. E. Kaplan, F. Ikeda, J. Ding, J. Schwartz, F. A. Nunes, H. J. Alter, and K.-M. Chang
Strain-Specific T-Cell Suppression and Protective Immunity in Patients with Chronic Hepatitis C Virus Infection
J. Virol., June 1, 2005; 79(11): 6976 - 6983.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
L. Howe, J. K. Craigo, C. J. Issel, and R. C. Montelaro
Specificity of serum neutralizing antibodies induced by transient immune suppression of inapparent carrier ponies infected with a neutralization-resistant equine infectious anemia virus envelope strain
J. Gen. Virol., January 1, 2005; 86(1): 139 - 149.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.