Altered positive selection due to corecognition of floppy peptide/MHC II conformers supports an integrative model of thymic selection
AUTOR(ES)
Viret, Christophe
FONTE
The National Academy of Sciences
RESUMO
Thymocytes bearing the Eα52-68/I-Ab complex-specific 1H3.1 αβ T cell antigen receptor are positively selected in Ab-Ep [Ab-Ep transgenic, invariant chain (Ii)−/−, I-Aβb−/−] mice, where I-Ab molecules present only Eα52-68. Although Ii reintroduction led to deletion, I-Aβb reintroduction disrupted positive selection. T cell antigen receptor transgenic Ab-Ep I-Aβb+ mice had a large thymus with an increased absolute number of CD4+CD8+ cells and no overt signs of deletion. Unlike Ab-Ep Ii+ antigen-presenting cells, Ab-Ep I-Aβb+ antigen-presenting cells did not activate 1H3.1 T cells. However, their capacity to present Eα52-68 was intact. Thus, positive selection of 1H3.1 thymocytes on the tight compact Eα52-68/I-Ab complex is neutralized by the corecognition of loose compact self-peptide/I-Ab conformers that do not interfere with the cognate activation of mature 1H3.1 T cells. The data support the notion that the integration of distinct signals generated by the simultaneous recognition of multiple self-peptide/MHC complexes directs intrathymic selection of T cells.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=154349Documentos Relacionados
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