Skip Navigation

This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (36)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Chidgey, A.
Right arrow Articles by Boyd, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chidgey, A.
Right arrow Articles by Boyd, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

International Immunology, Vol 9, 1527-1536, Copyright © 1997 by Oxford University Press

ARTICLES

Agonist peptide modulates T cell selection thresholds through qualitative and quantitative shifts in CD8 co-receptor expression

A Chidgey and R Boyd
Department of Pathology and Immunology, Monash Medical School, Prahran, Melbourne, Australia.

Engagement of the TCR is a pivotal step in thymocyte development, ultimately resulting in the survival (positive selection) or loss (negative selection) of developing T cells. The roles of peptides and stromal cell interactions necessary for these selection events, however, are still poorly understood. To investigate the effects of agonist peptide in positive selection, we used a novel cell suspension model for in vitro thymic positive selection in adults. Target thymocytes from H-2Db-restricted TCR transgenic mice, specific to the lymphocytic choriomeningitis virus (LCMV) peptide bred on a non- selecting MHC background (H-2d or TAP-1-/-), were co-cultured with freshly isolated H-2b thymic stromal cells. In the presence of selecting stroma the nominal agonist LCMV peptide induced apoptosis at high concentrations and at low concentrations enhanced the efficiency of positive selection both in numbers of cells 'rescued' and kinetics of appearance of selected single-positive cells. We further illustrate down-modulation of CD8 alpha beta or CD8 beta at high but non-deleting concentrations of agonist peptide. This highlights the ability of the T cell, within the window of positive selection, to modify surface co- receptors both qualitatively and quantitatively in response to increasing avidity TCR-peptide-MHC interactions. The direct consequence of this would be to lower the total signaling events below the threshold for apoptosis induction. Hence if self peptide were not presented in sufficient quantities in the thymus, autoreactive cells may escape deletion and may actually be positively selected.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Immunol.Home page
T. L. Denning, S. Granger, D. Mucida, R. Graddy, G. Leclercq, W. Zhang, K. Honey, J. P. Rasmussen, H. Cheroutre, A. Y. Rudensky, et al.
Mouse TCR{alpha}beta+CD8{alpha}{alpha} Intraepithelial Lymphocytes Express Genes That Down-Regulate Their Antigen Reactivity and Suppress Immune Responses
J. Immunol., April 1, 2007; 178(7): 4230 - 4239.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Kienzle, S. Olver, K. Buttigieg, P. Groves, M. L. Janas, A. Baz, and A. Kelso
Progressive Differentiation and Commitment of CD8+ T Cells to a Poorly Cytolytic CD8low Phenotype in the Presence of IL-4
J. Immunol., February 15, 2005; 174(4): 2021 - 2029.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. A. Baldwin, K. A. Hogquist, and S. C. Jameson
The Fourth Way? Harnessing Aggressive Tendencies in the Thymus
J. Immunol., December 1, 2004; 173(11): 6515 - 6520.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
L. T. Madakamutil, U. Christen, C. J. Lena, Y. Wang-Zhu, A. Attinger, M. Sundarrajan, W. Ellmeier, M. G. von Herrath, P. Jensen, D. R. Littman, et al.
CD8{alpha}{alpha}-Mediated Survival and Differentiation of CD8 Memory T Cell Precursors
Science, April 23, 2004; 304(5670): 590 - 593.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
G. L. Stephens, J. D. Ashwell, and L. Ignatowicz
Mutually antagonistic signals regulate selection of the T cell repertoire
Int. Immunol., May 1, 2003; 15(5): 623 - 632.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A. J. Leishman, O. V. Naidenko, A. Attinger, F. Koning, C. J. Lena, Y. Xiong, H.-C. Chang, E. Reinherz, M. Kronenberg, and H. Cheroutre
T Cell Responses Modulated Through Interaction Between CD8alpha alpha and the Nonclassical MHC Class I Molecule, TL
Science, November 30, 2001; 294(5548): 1936 - 1939.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. E. Stefanski, D. Mayerova, S. C. Jameson, and K. A. Hogquist
A Low Affinity TCR Ligand Restores Positive Selection of CD8+ T Cells In Vivo
J. Immunol., June 1, 2001; 166(11): 6602 - 6607.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. E. Berg, S. Irion, S. Kattman, M. F. Princiotta, and U. D. Staerz
A Physiological Ligand of Positive Selection Is Recognized as a Weak Agonist
J. Immunol., October 15, 2000; 165(8): 4209 - 4216.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
P. W. Zandstra, D. A. Lauffenburger, and C. J. Eaves
A ligand-receptor signaling threshold model of stem cell differentiation control: a biologically conserved mechanism applicable to hematopoiesis
Blood, August 15, 2000; 96(4): 1215 - 1222.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. E. Stefanski, S. C. Jameson, and K. A. Hogquist
Positive Selection Is Limited by Available Peptide-Dependent MHC Conformations
J. Immunol., April 1, 2000; 164(7): 3519 - 3526.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. Reali, R. Guerrini, M. Marastoni, R. Tomatis, M. Grazia Masucci, S. Traniello, and R. Gavioli
A Single Specific Amino Acid Residue in Peptide Antigens Is Sufficient to Activate Memory CTL: Potential Role of Cross-Reactive Peptides in Memory T Cell Maintenance
J. Immunol., January 1, 1999; 162(1): 106 - 113.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Mariathasan, M. F. Bachmann, D. Bouchard, T. Ohteki, and P. S. Ohashi
Degree of TCR Internalization and Ca2+ Flux Correlates with Thymocyte Selection
J. Immunol., December 1, 1998; 161(11): 6030 - 6037.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. A. Hogquist and J. L. Bonnevier
Development of Peptide-Selected CD8 T Cells in Fetal Thymic Organ Culture Occurs via the Conventional Pathway
J. Immunol., October 15, 1998; 161(8): 3896 - 3901.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Boyd, I. Kozieradzki, A. Chidgey, H.-W. Mittrucker, D. Bouchard, E. Timms, K. Kishihara, C. J. Ong, D. Chui, J. D. Marth, et al.
Receptor-Specific Allelic Exclusion of TCRV{alpha}-Chains During Development
J. Immunol., August 15, 1998; 161(4): 1718 - 1727.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
O. Williams, R. Tarazona, A. Wack, N. Harker, K. Roderick, and D. Kioussis
Interactions with multiple peptide ligands determine the fate of developing thymocytes
PNAS, May 12, 1998; 95(10): 5706 - 5711.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.