Abstract
DURING positive selection, developing thymocytes are rescued from programmed cell death by T-cell receptor (TCR)-mediated recognition of major histocompatibility complex (MHC) molecules1–3. MHC-bound peptides contribute to this process4–8. Recently we identified individual MHC-binding peptides which can induce positive selection of a single TCR9. Here we examine peptide fine specificity in positive selection. These data suggest that a direct TCR–peptide interaction occurs during this event, and strengthens the correlation between selecting peptides and TCR antagonists9,10. Certain positively selecting peptides are weakly antigenic9. We demonstrate that thymocytes 'educated' on such a peptide are specifically non-responsive to it and have decreased CDS expression levels. Similar reduction of CDS expression on mature T cells converts a TCR agonist into a TCR antagonist. These data indicate that thymocytes may maintain self-tolerance towards a positively selecting ligand by regulating co-receptor expression.
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Jameson, S., Hogquist, K. & Bevan, M. Specificity and flexibility in thymic selection. Nature 369, 750–752 (1994). https://doi.org/10.1038/369750a0
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DOI: https://doi.org/10.1038/369750a0
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