It’s the Peptide-MHC Affinity, Stupid (original) (raw)

“…However, experimental models have shown that the process of negative selection is exquisitely efficient and even a postselection repertoire consisting of more than 10% auto-reactive TCRs can be efficiently purged by rare antigen-positive medullary antigen presenting cells (APCs) [7,8]. If this were also the case for the human thymus, it would argue against the notion that overt positive selection of MART-1 [26][27][28][29][30][31][32][33][34][35] -specific CD8 + T cells alone could explain their unusually high frequency. Although quantitative aspects of positive selection cannot be directly addressed experimentally in humans, the prerequisites for tolerance induction, i.e.…”

Section: Introductionmentioning

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“…However, experimental models have shown that the process of negative selection is exquisitely efficient and even a postselection repertoire consisting of more than 10% auto-reactive TCRs can be efficiently purged by rare antigen-positive medullary antigen presenting cells (APCs) [7,8]. If this were also the case for the human thymus, it would argue against the notion that overt positive selection of MART-1 [26][27][28][29][30][31][32][33][34][35] -specific CD8 + T cells alone could explain their unusually high frequency. Although quantitative aspects of positive selection cannot be directly addressed experimentally in humans, the prerequisites for tolerance induction, i.e.…”

Section: Introductionmentioning

“…+ T cells specific to the peptide-MHC class I complex and MART-1 [26][27][28][29][30][31][32][33][34][35] -HLA-A2, are about 100 times more frequent in healthy individuals than T cells specific to other self-antigens [3]. This high frequency could be due either to an increased thymic output or to peripheral T cell expansion.…”

Section: Introductionmentioning

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