The impact of MHC class I dose on development and maintenance of the polyclonal naive CD8+ T cell repertoire

Xavier Y. X. Sng, Jasmine Li, Pirooz Zareie, Lisa M. Assmus, Jason K. C. Lee, Claerwen M. Jones, Stephen J. Turner, Stephen R. Daley, Kylie M. Quinn, Nicole L. La Gruta

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

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-7Ra. 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.

Original languageEnglish
Pages (from-to)3108-3116
Number of pages9
JournalJournal of Immunology
Volume204
Issue number12
DOIs
Publication statusPublished - 15 Jun 2020

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