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    Positive Selection of Cd4+ T Cells Is Induced in Vivo by Agonist and Inhibited by Antagonist Peptides

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    Authors
    Kraj, Piotr
    Pacholczyk, Rafal
    Ignatowicz, Hanna
    Kisielow, Pawel
    Jensen, Peter
    Ignatowicz, Leszek
    Issue Date
    2001-08-20
    URI
    http://hdl.handle.net/10675.2/554
    
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    Abstract
    The nature of peptides that positively select T cells in the thymus remains poorly defined. Here we report an in vivo model to study the mechanisms of positive selection of CD4+ T cells. We have restored positive selection of TCR transgenic CD4+ thymocytes, arrested at the CD4+CD8+ stage, due to the lack of the endogenously selecting peptide(s), in mice deficient for H2-M and invariant chain. A single injection of soluble agonist peptide(s) initiated positive selection of CD4+ transgenic T cells that lasted for up to 14 days. Positively selected CD4+ T cells repopulated peripheral lymphoid organs and could respond to the antigenic peptide. Furthermore, coinjection of the antagonist peptide significantly inhibited agonist-driven positive selection. Hence, contrary to the prevailing view, positive selection of CD4+ thymocytes can be induced in vivo by agonist peptides and may be a result of accumulation of signals from TCR engaged by different peptides bound to major histocompatibility complex class II molecules. We have also identified a candidate natural agonist peptide that induces positive selection of CD4+ TCR transgenic thymocytes.
    Citation
    J Exp Med. 2001 Aug 20; 194(4):407-416
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