The Impact of MHC Class I Dose on Development and Maintenance of the Polyclonal Naive CD8+ T Cell Repertoire
| Autor: | Xavier Y.X. Sng, Claerwen M. Jones, Stephen J. Turner, Stephen R. Daley, Jason K.C. Lee, Pirooz Zareie, Kylie M. Quinn, Lisa M Assmus, Jasmine Li, Nicole L. La Gruta |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 204:3108-3116 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Naive CD8+ T cell survival in the periphery is critically dependent on tonic TCR signaling through peptide + MHC class I (MHCI) recognition; however, little is known about how natural variation in MHCI levels impacts the naive CD8+ T cell repertoire. Using mice that are hemizygous or homozygous for a single MHCI allele, we showed that despite a reduction in peripheral CD8+ T cell numbers of ∼50% in MHCI hemizygous mice, MHCI levels had no notable impact on the rate of thymic generation or emigration of CD8 single-positive T cells. Moreover, the peripheral T cell repertoire in hemizygous mice showed selective retention of T cell clonotypes with a greater competitive advantage as evidenced by increased expression of CD5 and IL-7Rα. The qualitative superiority of CD8+ T cells retained in hemizygous mice was also seen during influenza A virus infection, in which epitope-specific CD8+ T cells from hemizygous mice had a higher avidity for pMHCI and increased cytokine polyfunctionality, despite a reduced response magnitude. Collectively, this study suggests that natural variation in MHCI expression levels has a notable and biologically relevant impact on the maintenance, but not generation, of the naive CD8+ T cell repertoire. |
| Databáze: | OpenAIRE |
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