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    Promiscuous thymic expression of an autoantigen gene does not result in negative selection of pathogenic T cells

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    Author
    Allen, S; Read, S; DiPaolo, R; McHugh, RS; Shevach, EM; Gleeson, PA; van Driel, IR
    Date
    2005-11-01
    Source Title
    JOURNAL OF IMMUNOLOGY
    Publisher
    AMER ASSOC IMMUNOLOGISTS
    University of Melbourne Author/s
    ALLEN, STACEY; Gleeson, Paul; van Driel, Ian; READ, SIMON
    Affiliation
    Biochemistry And Molecular Biology
    Metadata
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    Document Type
    Journal Article
    Citations
    Allen, S., Read, S., DiPaolo, R., McHugh, R. S., Shevach, E. M., Gleeson, P. A. & van Driel, I. R. (2005). Promiscuous thymic expression of an autoantigen gene does not result in negative selection of pathogenic T cells. JOURNAL OF IMMUNOLOGY, 175 (9), pp.5759-5764. https://doi.org/10.4049/jimmunol.175.9.5759.
    Access Status
    This item is currently not available from this repository
    URI
    http://hdl.handle.net/11343/26622
    DOI
    10.4049/jimmunol.175.9.5759
    Description

    C1 - Journal Articles Refereed

    Abstract
    "Promiscuous" thymic expression of peripheral autoantigens can contribute to immunological tolerance in some cases. However, in this study we show that thymic mRNA expression alone cannot predict a contribution to thymic tolerance. Autoimmune gastritis is caused by CD4+ T cells directed to the alpha (H/Kalpha) and beta (H/Kbeta) subunits of the gastric membrane protein the H+/K+ ATPase. H/Kalpha mRNA is expressed in the thymus, but H/Kbeta expression is barely detectable. In this study, we demonstrate that thymic H/Kalpha in wild-type mice or mice that overexpressed H/Kalpha did not result in negative selection of pathogenic anti-H/Kalpha T cells. However, negative selection of anti-H/Kalpha T cells did occur if H/Kbeta was artificially overexpressed in the thymus. Given that H/Kalpha cannot be exported from the endoplasmic reticulum and is rapidly degraded in the absence of H/Kbeta, we conclude that H/Kalpha epitopes are unable to access MHC class II loading compartments in cells of the normal thymus. This work, taken together with our previous studies, highlights that thymic autoantigen expression does not necessarily result in the induction of tolerance.
    Keywords
    Biochemistry and Cell Biology not elsewhere classified ; Biological Sciences

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