HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dave, V. P. Articles by Kappes, D. J. Search for Related Content PubMed PubMed Citation Articles by Dave, V. P. Articles by Kappes, D. J.

Limiting TCR Expression Leads to Quantitative But Not Qualitative Changes in Thymic Selection¹

Fox Chase Cancer Center, Philadelphia, PA 19111

Thymic selection is controlled in part by the avidity of the interaction between thymocytes and APCs. In agreement, the selective outcome can be modulated by altering the expression levels of selecting ligands on APCs. Here we test the converse proposition, i.e., whether changing TCR levels on thymocytes can alter the selective outcome. To this end, we have generated mice in which all thymocytes express two transgenic TCRs simultaneously (dual TCR-expressing (DTE) mice), the class I-restricted HY TCR and the class II-restricted AND TCR. Due to mutual dilution, surface expression levels of the two individual transgenic TCRs are diminished in DTE relative to single TCR-expressing mice. We find that thymic selection is highly sensitive to these reductions in TCR surface expression. Positive selection mediated by the AND and HY TCRs is severely impaired or abolished, respectively. Negative selection of the HY TCR in male DTE mice is also partly blocked, leading to the appearance of significant numbers of double positive thymocytes. Also, in the periphery of male, but not female, DTE mice, substantial numbers of single positive CD8^bright cells accumulate, which are positively selected in the thymus but by a highly inefficient hemopoietic cell-dependent process. Overall our results favor the interpretation that the outcome of thymic selection is not determined solely by avidity and the resulting signal intensity, but is also constrained by other factors such as the nature of the ligand and/or its presentation by different subsets of APCs.

This article has been cited by other articles:

				J.-F. Brodeur, S. Li, O. Damlaj, and V. P. Dave Expression of fully assembled TCR-CD3 complex on double positive thymocytes: synergistic role for the PRS and ER retention motifs in the intra-cytoplasmic tail of CD3{varepsilon} Int. Immunol., December 1, 2009; 21(12): 1317 - 1327. [Abstract] [Full Text] [PDF]

				L. M. Relland, M. K. Mishra, D. Haribhai, B. Edwards, J. Ziegelbauer, and C. B. Williams Affinity-Based Selection of Regulatory T Cells Occurs Independent of Agonist-Mediated Induction of Foxp3 Expression J. Immunol., February 1, 2009; 182(3): 1341 - 1350. [Abstract] [Full Text] [PDF]

				A. Warmflash, M. Weigert, and A. R. Dinner Control of Genotypic Allelic Inclusion through TCR Surface Expression J. Immunol., November 15, 2005; 175(10): 6412 - 6419. [Abstract] [Full Text] [PDF]

				M. T. Fisher, M. Nagarkatti, and P. S. Nagarkatti 2,3,7,8-Tetrachlorodibenzo-p-dioxin Enhances Negative Selection of T Cells in the Thymus but Allows Autoreactive T Cells to Escape Deletion and Migrate to the Periphery Mol. Pharmacol., January 1, 2005; 67(1): 327 - 335. [Abstract] [Full Text] [PDF]

				H. D. Lacorazza and J. Nikolich-Zugich Exclusion and Inclusion of TCR{alpha} Proteins during T Cell Development in TCR-Transgenic and Normal Mice J. Immunol., November 1, 2004; 173(9): 5591 - 5600. [Abstract] [Full Text] [PDF]

				N. Legrand and A. A. Freitas CD8+ T Lymphocytes in Double {alpha}{beta} TCR Transgenic Mice. I. TCR Expression and Thymus Selection in the Absence or in the Presence of Self-Antigen J. Immunol., December 1, 2001; 167(11): 6150 - 6157. [Abstract] [Full Text] [PDF]

				N. Legrand and A. A. Freitas CD8+ T Lymphocytes in Double {alpha}{beta} TCR Transgenic Mice. II. Competitive Fitness of Dual {alpha}{beta} TCR CD8+ T Lymphocytes in the Peripheral Pools J. Immunol., December 1, 2001; 167(11): 6158 - 6164. [Abstract] [Full Text] [PDF]

				N. Watanabe, H. Arase, M. Onodera, P. S. Ohashi, and T. Saito The Quantity of TCR Signal Determines Positive Selection and Lineage Commitment of T Cells J. Immunol., December 1, 2000; 165(11): 6252 - 6261. [Abstract] [Full Text] [PDF]

				S. Trop, M. Rhodes, D. L. Wiest, P. Hugo, and J. C. Zuniga-Pflucker Competitive Displacement of pT{alpha} by TCR-{alpha} During TCR Assembly Prevents Surface Coexpression of Pre-TCR and {alpha}{beta} TCR J. Immunol., November 15, 2000; 165(10): 5566 - 5572. [Abstract] [Full Text] [PDF]

				C. Menne, J. P. H. Lauritsen, J. Dietrich, J. Kastrup, A.-M. K. Wegener, N. Odum, and C. Geisler Ceramide-Induced TCR Up-Regulation J. Immunol., September 15, 2000; 165(6): 3065 - 3072. [Abstract] [Full Text] [PDF]

				S. Trop, J. Charron, C. Arguin, and P. Hugo Thymic Selection Generates T Cells Expressing Self-Reactive TCRs in the Absence of CD45 J. Immunol., September 15, 2000; 165(6): 3073 - 3079. [Abstract] [Full Text] [PDF]