Positive and negative selection of an antigen receptor on T cells in transgenic mice (original) (raw)

Nature volume 336, pages 73–76 (1988)Cite this article

Abstract

The T-cell repertoire found in the periphery is thought to be shaped by two developmental events in the thymus that involve the antigen receptors of T lymphocytes. First, interactions between T cells and major histocompatibility complex (MHC) molecules select a T-cell repertoire skewed towards recognition of antigens in the context of self-MHC molecules1–5. In addition, T cells that react strongly to self-MHC molecules are eliminated by a process called self-tolerance6–10. We have recently described transgenic mice expressing the αβ T-cell receptor from the cytotoxic T lymphocyte 2C (ref. 11). The clone 2C was derived from a BALB.B (H–2b) anti-BALB/c (H–2d) mixed lymphocyte culture and is specific for the Ld class I MHC antigen. In transgenic H–2b mice, a large fraction of T cells in the periphery expressed the 2C T-cell receptor. These T cells were predominantly CD4-CD8+ and were able to specifically lyse target cells bearing Ld. We now report that in the periphery of transgenic mice expressing Ld, functional T cells bearing the 2C T-cell receptor were deleted. This elimination of autoreactive T cells appears to take place at or before the CD4+CD8+ stage in thymocyte development. In addition, we report that in H–28 mice, a non-autoreactive target haplotype, large numbers of CDS* T cells bearing the 2C T-cell receptor were not found, providing strong evidence for the positive selection of the 2C T-cell receptor specificity by H–2b molecules.

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Author notes

  1. John H. Russell: Pharmacology, St Louis, Missouri 63110, USA
  2. David M. Kranz: Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute, Departments of Medicine, Genetics, Microbiology and Immunology, Washington University School of Medicine, St Louis, Missouri, 63110, USA
    William C. Sha, Christopher A. Nelson, Rodney D. Newberry, David M. Kranz, John H. Russell & Dennis Y. Loh

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  1. William C. Sha
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  2. Christopher A. Nelson
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  3. Rodney D. Newberry
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  4. David M. Kranz
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  5. John H. Russell
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  6. Dennis Y. Loh
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Sha, W., Nelson, C., Newberry, R. et al. Positive and negative selection of an antigen receptor on T cells in transgenic mice.Nature 336, 73–76 (1988). https://doi.org/10.1038/336073a0

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