Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 421K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Terrence, K. Articles by Fowlkes, B.J. Search for Related Content PubMed PubMed Citation Articles by Terrence, K. Articles by Fowlkes, B.J. Pubmed/NCBI databases Substance via MeSH Social Bookmarking                            What's this?

Original Article

Premature Expression of T Cell Receptor (Tcr)β Suppresses Tcr Gene Rearrangement but Permits Development of Lineage T Cells

^a Laboratory of Cellular and Molecular Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0420
Bldg. 4, Rm. 111, Laboratory of Cellular and Molecular Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0420.301-402-4891301-496-5530

bfowlkes{at}nih.gov

The T cell receptor (TCR) and the pre-TCR promote survival and maturation of early thymocyte precursors. Whether these receptors also influence versus β lineage determination is less clear. We show here that TCR gene rearrangements are suppressed in TCRβ transgenic mice when the TCRβ is expressed early in T cell development. This situation offers the opportunity to examine the outcome of versus β T lineage commitment when only the TCRβ is expressed. We find that precursor thymocytes expressing TCRβ not only mature in the β pathway as expected, but also as CD4^–CD8^– T cells with properties of lineage cells. In TCRβ transgenic mice, in which the transgenic receptor is expressed relatively late, TCR rearrangements occur normally such that TCRβ⁺CD4^–CD8^– cells co-express TCR. The results support the notion that TCRβ can substitute for TCR to permit a lineage choice and maturation in the lineage. The findings could fit a model in which lineage commitment is determined before or independent of TCR gene rearrangement. However, these results could be compatible with a model in which distinct signals bias lineage choice and these signaling differences are not absolute or intrinsic to the specific TCR structure.

Key Words: lineage commitment • TCR transgenic mice • thymus • differentiation • positive selection

Abbreviations used in this paper: APC, allophycocyanin; β₂m, β₂-microglobulin; B6, C57BL/6; B10, C57BL/10; CsA, cyclosporine A; HSA, heat stable antigen; RAG, recombination activating gene; TCRβDN, TCRβ⁺CD4^–CD8^–.

K. Terrence and C.P. Pavlovich contributed equally to this work.

© 2000 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Leung, M. W.L., Shen, S., Lafaille, J. J. (2009). TCR-dependent differentiation of thymic Foxp3+ cells is limited to small clonal sizes. JEM 206: 2121-2130 [Abstract] [Full Text]  
• Shen, S., Lau, J., Zhu, M., Zou, J., Fuller, D., Li, Q.-j., Zhang, W. (2009). The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-{alpha} motif domain in thymic selection and T-cell activation. Blood 114: 74-84 [Abstract] [Full Text]  
• Kreslavsky, T., Garbe, A. I., Krueger, A., von Boehmer, H. (2008). T cell receptor-instructed {alpha}{beta} versus {gamma}{delta} lineage commitment revealed by single-cell analysis. JEM 205: 1173-1186 [Abstract] [Full Text]  
• Serwold, T., Hochedlinger, K., Inlay, M. A., Jaenisch, R., Weissman, I. L. (2007). Early TCR Expression and Aberrant T Cell Development in Mice with Endogenous Prerearranged T Cell Receptor Genes. J. Immunol. 179: 928-938 [Abstract] [Full Text]  
• Riera-Sans, L., Behrens, A. (2007). Regulation of {alpha}beta/{gamma}{delta} T Cell Development by the Activator Protein 1 Transcription Factor c-Jun. J. Immunol. 178: 5690-5700 [Abstract] [Full Text]  
• Leng, Q., Ge, Q., Nguyen, T., Eisen, H. N., Chen, J. (2007). Stage-dependent reactivity of thymocytes to self-peptide-MHC complexes. Proc. Natl. Acad. Sci. USA 104: 5038-5043 [Abstract] [Full Text]  
• Priatel, J. J., Chen, X., Dhanji, S., Abraham, N., Teh, H.-S. (2006). RasGRP1 Transmits Prodifferentiation TCR Signaling That Is Crucial for CD4 T Cell Development. J. Immunol. 177: 1470-1480 [Abstract] [Full Text]  
• Aifantis, I., Bassing, C. H., Garbe, A. I., Sawai, K., Alt, F. W., von Boehmer, H. (2006). The E{delta} enhancer controls the generation of CD4-CD8- {alpha}{beta}TCR-expressing T cells that can give rise to different lineages of {alpha}{beta} T cells. JEM 203: 1543-1550 [Abstract] [Full Text]  
• Garbe, A. I., Krueger, A., Gounari, F., Zuniga-Pflucker, J. C., von Boehmer, H. (2006). Differential synergy of Notch and T cell receptor signaling determines {alpha}{beta} versus {gamma}{delta} lineage fate. JEM 203: 1579-1590 [Abstract] [Full Text]  
• Wei, D. G., Curran, S. A., Savage, P. B., Teyton, L., Bendelac, A. (2006). Mechanisms imposing the V{beta} bias of V{alpha}14 natural killer T cells and consequences for microbial glycolipid recognition. JEM 203: 1197-1207 [Abstract] [Full Text]  
• Joachims, M. L., Chain, J. L., Hooker, S. W., Knott-Craig, C. J., Thompson, L. F. (2006). Human {alpha}beta and {gamma}{delta} Thymocyte Development: TCR Gene Rearrangements, Intracellular TCRbeta Expression, and {gamma}{delta} Developmental Potential--Differences between Men and Mice. J. Immunol. 176: 1543-1552 [Abstract] [Full Text]  
• Baldwin, T. A., Sandau, M. M., Jameson, S. C., Hogquist, K. A. (2005). The timing of TCR{alpha} expression critically influences T cell development and selection. JEM 202: 111-121 [Abstract] [Full Text]  
• Gerber, D., Boucontet, L., Pereira, P. (2004). Early Expression of a Functional TCR{beta} Chain Inhibits TCR{gamma} Gene Rearrangements without Altering the Frequency of TCR{gamma}{delta} Lineage Cells. J. Immunol. 173: 2516-2523 [Abstract] [Full Text]  
• Krotkova, A., Smith, E., Nerz, G., Falk, I., Eichmann, K. (2004). Delayed and Restricted Expression Limits Putative Instructional Opportunities of V{gamma}1.1/V{gamma}2 {gamma}{delta} TCR in {alpha}{beta}/{gamma}{delta} Lineage Choice in the Thymus. J. Immunol. 173: 25-32 [Abstract] [Full Text]  
• Erman, B., Guinter, T. I., Singer, A. (2004). Defined {alpha}{beta} T Cell Receptors with Distinct Ligand Specificities Do Not Require Those Ligands to Signal Double Negative Thymocyte Differentiation. JEM 199: 1719-1724 [Abstract] [Full Text]  
• Borowski, C., Li, X., Aifantis, I., Gounari, F., von Boehmer, H. (2004). Pre-TCR{alpha} and TCR{alpha} Are Not Interchangeable Partners of TCR{beta} during T Lymphocyte Development. JEM 199: 607-615 [Abstract] [Full Text]  
• Mayerova, D., Hogquist, K. A. (2004). Central Tolerance to Self-Antigen Expressed by Cortical Epithelial Cells. J. Immunol. 172: 851-856 [Abstract] [Full Text]  
• Mintern, J. D., Maurice, M. M., Ploegh, H. L., Schott, E. (2004). Thymic Selection and Peripheral Activation of CD8 T Cells by the Same Class I MHC/Peptide Complex. J. Immunol. 172: 699-708 [Abstract] [Full Text]  
• Blank, C., Brown, I., Marks, R., Nishimura, H., Honjo, T., Gajewski, T. F. (2003). Absence of Programmed Death Receptor 1 Alters Thymic Development and Enhances Generation of CD4/CD8 Double-Negative TCR-Transgenic T Cells. J. Immunol. 171: 4574-4581 [Abstract] [Full Text]  
• Holman, P. O., Walsh, E. R., Hogquist, K. A. (2003). The Central Tolerance Response to Male Antigen in Normal Mice Is Deletion and Not Receptor Editing. J. Immunol. 171: 4048-4053 [Abstract] [Full Text]  
• Haks, M. C., Belkowski, S. M., Ciofani, M., Rhodes, M., Lefebvre, J. M., Trop, S., Hugo, P., Zuniga-Pflucker, J. C., Wiest, D. L. (2003). Low Activation Threshold As a Mechanism for Ligand-Independent Signaling in Pre-T Cells. J. Immunol. 170: 2853-2861 [Abstract] [Full Text]  
• Boyer, O., Marodon, G., Cohen, J. L., Lejeune, L., Irinopoulou, T., Liblau, R., Bruneval, P., Klatzmann, D. (2002). Human CD4 Expression at the Late Single-Positive Stage of Thymic Development Supports T Cell Maturation and Peripheral Export in CD4-Deficient Mice. J. Immunol. 169: 4347-4353 [Abstract] [Full Text]  
• Terra, R., Labrecque, N., Perreault, C. (2002). Thymic and Extrathymic T Cell Development Pathways Follow Different Rules. J. Immunol. 169: 684-692 [Abstract] [Full Text]  
• Panigada, M., Porcellini, S., Barbier, E., Hoeflinger, S., Cazenave, P.-A., Gu, H., Band, H., von Boehmer, H., Grassi, F. (2002). Constitutive Endocytosis and Degradation of the Pre-T Cell Receptor. JEM 195: 1585-1597 [Abstract] [Full Text]  
• Legrand, N., Freitas, A. A. (2001). 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. 167: 6150-6157 [Abstract] [Full Text]  
• Lacorazza, H. D., Porritt, H. E., Nikolich-Zugich, J. (2001). Dysregulated Expression of Pre-T{alpha} Reveals the Opposite Effects of Pre-TCR at Successive Stages of T Cell Development. J. Immunol. 167: 5689-5696 [Abstract] [Full Text]  
• Petersson, K., Ivars, F. (2001). Early TCR {{alpha}}{{beta}} Expression Promotes Maturation of T Cells Expressing Fc{{epsilon}}RI{{gamma}} Containing TCR/CD3 Complexes. J. Immunol. 166: 6616-6624 [Abstract] [Full Text]  
• Kang, J., Volkmann, A., Raulet, D. H. (2001). Evidence That {gamma}{delta} versus {alpha}{beta} T Cell Fate Determination Is Initiated Independently of T Cell Receptor Signaling. JEM 193: 689-698 [Abstract] [Full Text]  
• Lacorazza, H. D., Tucek-Szabo, C., Vasovic, L. V., Remus, K., Nikolich-Zugich, J. (2001). Premature TCR{{alpha}}{{beta}} Expression and Signaling in Early Thymocytes Impair Thymocyte Expansion and Partially Block Their Development. J. Immunol. 166: 3184-3193 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS