Altered positive selection due to corecognition of floppy peptide/MHC II conformers supports an integrative model of thymic selection
| Autor: | Xin He, Christophe Viret, Charles A Janeway |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Multidisciplinary
Base Sequence biology Antigen processing Antigen presentation Histocompatibility Antigens Class II Antigen-Presenting Cells Thymus Gland Biological Sciences MHC restriction Major histocompatibility complex Molecular biology Mice Inbred C57BL Mice biology.protein Animals Cytotoxic T cell IL-2 receptor Antigen-presenting cell CD8 DNA Primers |
| Zdroj: | Proceedings of the National Academy of Sciences. 100:5354-5359 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0831129100 |
| Popis: | Thymocytes bearing the Eα52-68/I-A b complex-specific 1H3.1 αβ T cell antigen receptor are positively selected in Ab-Ep [Ab-Ep transgenic, invariant chain (Ii) −/− , I-Aβ b−/− ] mice, where I-A b molecules present only Eα52-68. Although Ii reintroduction led to deletion, I-Aβ b reintroduction disrupted positive selection. T cell antigen receptor transgenic Ab-Ep I-Aβ b+ 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-Aβ b+ 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-A b complex is neutralized by the corecognition of loose compact self-peptide/I-A b 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. |
| Databáze: | OpenAIRE |
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