J. Exp. Med., Volume 189, Number 1, January 4, 1999 13-24

A T Cell Receptor-specific Blockade of Positive Selection

By Kristin K. Baldwin,^* Philip A. Reay,^§ Lawren Wu,^* Andrew Farr, and Mark M. Davis^*

From the ^* Howard Hughes Medical Institute, and the Department of Microbiology and Immunology, Stanford University, Stanford, California 94305; the  Department of Biological Structure and Department of Immunology, School of Medicine, University of Washington, Seattle, Washington 98195; and the ^§ Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Headington, OX3 9DU, United Kingdom

To investigate the influence of endogenous peptides on the developmental processes that occur during thymocyte selection, we have used monoclonal antibodies that preferentially recognize the major histocompatibility complex (MHC) molecule I-E^k when it is bound to the moth cytochrome c peptide (88-103). One of these antibodies (G35) specifically blocks the positive selection of transgenic thymocytes expressing a T cell receptor that is reactive to this peptide- MHC complex. Furthermore, G35 does not block the differentiation of transgenic T cells bearing receptors for a different I-E^k-peptide complex. This antibody recognizes a subset of endogenous I-E^k-peptide complexes found on a significant fraction of thymic antigen-presenting cells, including cortical and medullary epithelial cells. The sensitivity of G35 to minor alterations in peptide sequence suggests that the thymic peptide-MHC complexes that mediate the positive selection of a particular class II MHC-restricted thymocyte are structurally related to the complexes that can activate it in the periphery.

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

This article has been cited by other articles:

• Tseng, S.-Y., Liu, M., Dustin, M. L. (2005). CD80 Cytoplasmic Domain Controls Localization of CD28, CTLA-4, and Protein Kinase C{theta} in the Immunological Synapse. J. Immunol. 175: 7829-7836 [Abstract] [Full Text]  
• Deleo, J. A., Tanga, F. Y., Tawfik, V. L. (2004). Neuroimmune Activation and Neuroinflammation in Chronic Pain and Opioid Tolerance/Hyperalgesia. Neuroscientist 10: 40-52 [Abstract]  
• Viret, C., He, X., Janeway, C. A. Jr. (2003). Altered positive selection due to corecognition of floppy peptide/MHC II conformers supports an integrative model of thymic selection. Proc. Natl. Acad. Sci. USA 100: 5354-5359 [Abstract] [Full Text]  
• Viret, C., He, X., Janeway, C. A. Jr. (2001). Paradoxical intrathymic positive selection in mice with only a covalently presented agonist peptide. Proc. Natl. Acad. Sci. USA 10.1073/pnas.161274698v1 [Abstract] [Full Text]  
• Chung, D. H., Belyakov, I. M., Derby, M. A., Wang, J., Boyd, L. F., Berzofsky, J. A., Margulies, D. H. (2001). Competitive Inhibition In Vivo and Skewing of the T Cell Repertoire of Antigen-Specific CTL Priming by an Anti-Peptide-MHC Monoclonal Antibody. J. Immunol. 167: 699-707 [Abstract] [Full Text]  
• Viret, C., He, X., Janeway, C. A. Jr. (2000). On the Self-Referential Nature of Naive MHC Class II-Restricted T Cells. J. Immunol. 165: 6183-6192 [Abstract] [Full Text]  
• Fukui, Y., Oono, T., Cabaniols, J.-P., Nakao, K., Hirokawa, K., Inayoshi, A., Sanui, T., Kanellopoulos, J., Iwata, E., Noda, M., Katsuki, M., Kourilsky, P., Sasazuki, T. (2000). Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact. Proc. Natl. Acad. Sci. USA 10.1073/pnas.250470797v1 [Abstract] [Full Text]  
• Reay, P. A., Matsui, K., Haase, K., Wulfing, C., Chien, Y.-H., Davis, M. M. (2000). Determination of the Relationship Between T Cell Responsiveness and the Number of MHC-Peptide Complexes Using Specific Monoclonal Antibodies. J. Immunol. 164: 5626-5634 [Abstract] [Full Text]  
• Krogsgaard, M., Wucherpfennig, K. W., Canella, B., Hansen, B. E., Svejgaard, A., Pyrdol, J., Ditzel, H., Raine, C., Engberg, J., Fugger, L. (2000). Visualization of Myelin Basic Protein (MBP) T Cell Epitopes in Multiple Sclerosis Lesions using a Monoclonal Antibody Specific for the Human Histocompatibility Leukocyte Antigen (HLA)-DR2-MBP 85-99 Complex. JEM 191: 1395-1412 [Abstract] [Full Text]  
• Baldwin, K. K., Trenchak, B. P., Altman, J. D., Davis3, M. M. (1999). Negative Selection of T Cells Occurs Throughout Thymic Development. J. Immunol. 163: 689-698 [Abstract] [Full Text]  
• Viret, C., He, X., Janeway, C. A. Jr. (2001). Paradoxical intrathymic positive selection in mice with only a covalently presented agonist peptide. Proc. Natl. Acad. Sci. USA 98: 9243-9248 [Abstract] [Full Text]  
• Fukui, Y., Oono, T., Cabaniols, J.-P., Nakao, K., Hirokawa, K., Inayoshi, A., Sanui, T., Kanellopoulos, J., Iwata, E., Noda, M., Katsuki, M., Kourilsky, P., Sasazuki, T. (2000). Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact. Proc. Natl. Acad. Sci. USA 97: 13760-13765 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS