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. |