| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121;
Oregon Health and Science University Vaccine and Gene Therapy Institute, Beaverton, OR 97006;
Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037; and
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322
Negative selection is designed to purge the immune system of high-avidity, self-reactive T cells and thereby protect the host from overt autoimmunity. In this in vivo viral infection model, we show that there is a previously unappreciated dichotomy involved in negative selection in which high-avidity CD8+ T cells specific for a dominant epitope are eliminated, whereas T cells specific for a subdominant epitope on the same protein preferentially escape deletion. Although this resulted in significant skewing of immunodominance and a substantial depletion of the most promiscuous T cells, thymic and/or peripheral deletion of high-avidity CD8+ T cells was not accompanied by any major change in the TCR V
gene family usage or an absolute deletion of a single preferred complementarity-determining region 3 length polymorphism. This suggests that negative selection allows high-avidity CD8+ T cells specific for subdominant or cryptic epitopes to persist while effectively deleting high-avidity T cells specific for dominant epitopes. By allowing the escape of subdominant T cells, this process still preserves a relatively broad peripheral TCR repertoire that can actively participate in antiviral and/or autoreactive immune responses.
This article has been cited by other articles:
|
|
 |
|
  M. M. Lauwen, S. Zwaveling, L. de Quartel, S. C. Ferreira Mota, J. A.C. Grashorn, C. J.M. Melief, S. H. van der Burg, and R. Offringa Self-Tolerance Does Not Restrict the CD4+ T-Helper Response against the p53 Tumor Antigen Cancer Res., February 1, 2008; 68(3): 893 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Otahal, B. B. Knowles, S. S. Tevethia, and T. D. Schell Anti-CD40 Conditioning Enhances the TCD8 Response to a Highly Tolerogenic Epitope and Subsequent Immunotherapy of Simian Virus 40 T Antigen-Induced Pancreatic Tumors J. Immunol., November 15, 2007; 179(10): 6686 - 6695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. N. Messingham, V. P. Badovinac, A. Jabbari, and J. T. Harty A Role for IFN-{gamma} from Antigen-Specific CD8+ T Cells in Protective Immunity to Listeria monocytogenes J. Immunol., August 15, 2007; 179(4): 2457 - 2466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Assarsson, J. Sidney, C. Oseroff, V. Pasquetto, H.-H. Bui, N. Frahm, C. Brander, B. Peters, H. Grey, and A. Sette A Quantitative Analysis of the Variables Affecting the Repertoire of T Cell Specificities Recognized after Vaccinia Virus Infection J. Immunol., June 15, 2007; 178(12): 7890 - 7901. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lee, S. A. Miller, D. W. Wright, M. T. Rock, and J. E. Crowe Jr. Tissue-Specific Regulation of CD8+ T-Lymphocyte Immunodominance in Respiratory Syncytial Virus Infection J. Virol., March 1, 2007; 81(5): 2349 - 2358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bruder, A. K. Nussbaum, D. M. Gakamsky, M. Schirle, S. Stevanovic, H. Singh-Jasuja, A. Darji, T. Chakraborty, H. Schild, I. Pecht, et al. Multiple synergizing factors contribute to the strength of the CD8+ T cell response against listeriolysin O Int. Immunol., January 1, 2006; 18(1): 89 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Singh, M. E. Dominiecki, E. M. Jaffee, and Y. Paterson Fusion to Listeriolysin O and Delivery by Listeria monocytogenes Enhances the Immunogenicity of HER-2/neu and Reveals Subdominant Epitopes in the FVB/N Mouse J. Immunol., September 15, 2005; 175(6): 3663 - 3673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Basler, N. Youhnovski, M. van den Broek, M. Przybylski, and M. Groettrup Immunoproteasomes Down-Regulate Presentation of a Subdominant T Cell Epitope from Lymphocytic Choriomeningitis Virus J. Immunol., September 15, 2004; 173(6): 3925 - 3934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. Schell In Vivo Expansion of the Residual Tumor Antigen-Specific CD8+ T Lymphocytes That Survive Negative Selection in Simian Virus 40 T-Antigen-Transgenic Mice J. Virol., February 15, 2004; 78(4): 1751 - 1762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. De Boer, D. Homann, and A. S. Perelson Different Dynamics of CD4+ and CD8+ T Cell Responses During and After Acute Lymphocytic Choriomeningitis Virus Infection J. Immunol., October 15, 2003; 171(8): 3928 - 3935. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
