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The Journal of Immunology, Vol 148, Issue 11 3342-3353, Copyright © 1992 by American Association of Immunologists
ARTICLES |
J Kaye, NJ Vasquez and SM Hedrick
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
The Ag receptor (TCR) on T lymphocytes has been shown to be specific for foreign antigenic peptides bound to MHC-encoded molecules. During T cell differentiation in the thymus this same TCR mediates the recognition of MHC molecules in the absence of foreign Ag, a process termed positive selection. To analyze the structural relationship between MHC-restricted Ag recognition and positive selection, we characterized two different transgenic lines of mice bearing TCR specific for pigeon cytochrome c and the Ek class II MHC molecule. The two TCR expressed in these animals differed by only one amino acid in the V-J junction of the alpha-chain. In vitro, we find that this TCR difference alters Ag fine specificity. Analysis of transgenic animals demonstrates that this change in the putative third complementarity determining region of the TCR also alters the specificity of positive selection in the thymus. These results suggest that the diversity of a TCR region that can be shown to affect the specificity of foreign Ag recognition may be influenced by selection in the thymus. The findings presented here are discussed in relation to the possible role of self- peptides in positive selection.
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C.-P. Liu, D. Parker, J. Kappler, and P. Marrack Selection of Antigen-specific T Cells by a Single IEk Peptide Combination J. Exp. Med., November 3, 1997; 186(9): 1441 - 1450. [Abstract] [Full Text] [PDF]
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A. Alam, M. Y. Braun, F. Hartgers, S. Lesage, L. Cohen, P. Hugo, F. Denis, and R.-P. Sekaly Specific Activation of the Cysteine Protease CPP32 during the Negative Selection of T Cells in the Thymus J. Exp. Med., November 3, 1997; 186(9): 1503 - 1512. [Abstract] [Full Text] [PDF]
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E Sebzda, V. Wallace, J Mayer, R. Yeung, T. Mak, and P. Ohashi Positive and negative thymocyte selection induced by different concentrations of a single peptide Science, March 18, 1994; 263(5153): 1615 - 1618. [Abstract] [PDF]
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D. H. Fremont, S. Dai, H. Chiang, F. Crawford, P. Marrack, and J. Kappler Structural Basis of Cytochrome c Presentation by IEk J. Exp. Med., April 15, 2002; 195(8): 1043 - 1052. [Abstract] [Full Text] [PDF]
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