Expert Reviews in Molecular Medicine: http://www.expertreviews.org/
Accession information: Vol. 5; 28 March 2003 Back to article abstract
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Split tolerance for p53

Matthias Theobald and Rienk Offringa

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Figure 3. Split tolerance for p53. (a) In thymic antigen-presenting cells (APCs), as in the vast majority of normal somatic cells, wild-type (WT) p53 exhibits a very short half-life of fewer than 30 minutes. Degradation of p53 is mediated through the ubiquitin/proteasome-dependent pathway, which results in efficient delivery of p53-derived peptide antigens for loading onto major histocompatibility complex (MHC) class I molecules. During T-cell selection in the thymus, those thymocytes that recognise p53 epitopes in the context of MHC class I with high avidity are likely to be deleted, in order to maintain self-tolerance in the periphery. (b) Because of the prevalence of p53 presentation via MHC class I, p53-derived peptides are unlikely to become available either for direct presentation in MHC class II on this APC or for cross-presentation on other APCs. Thus, thymocytes that would be capable of recognising p53 in the context of MHC class II do not find their ligand in the thymus and can make it to the periphery (fig003mtm).

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