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Publication : The Impact of MHC Class I Dose on Development and Maintenance of the Polyclonal Naive CD8<sup>+</sup> T Cell Repertoire.

First Author  Sng XYX Year  2020
Journal  J Immunol Volume  204
Issue  12 Pages  3108-3116
PubMed ID  32341060 Mgi Jnum  J:293387
Mgi Id  MGI:6445056 Doi  10.4049/jimmunol.2000081
Citation  Sng XYX, et al. (2020) The Impact of MHC Class I Dose on Development and Maintenance of the Polyclonal Naive CD8(+) T Cell Repertoire. J Immunol 204(12):3108-3116
abstractText  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 approximately 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-7Ralpha. 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.
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