Biology subjects

Robey, E.

Publications and source records attributed to Robey, E..

3 recordsLinked to original sources

bioRxiv2025

Preselection CD4+CD8+ thymocytes modulate TCR responsiveness following TCRβ selection

Modulation of TCR sensitivity during positive selection is critical to avoid negative selection and direct thymocytes into their appropriate lineage. Thymocytes just prior to positive selection (preselection) are highly responsive to low affinity self-ligands and are also actively rearranging their TCR locus as they await a positive selection signal. Preselection DP thymocytes were thought to be relatively homogeneous and TCR modulation during this stage had not been previously described. Here we provide evidence for progressive gene expression changes within the preselection DP thymocyte population that correlates with a gradual loss of TCR responsiveness and a defect in upregulating TCR target genes associated with the CD4 fate. We relate these observations to the link between positive selection and T cell lineage commitment.

immunology↗

bioRxiv2022

The promiscuous development of an unconventional Qa1b-restricted T cell population

MHC-E restricted CD8 T cells show promise in vaccine settings, but their development and specificity remain poorly understood. Here we focus on a CD8 T cell population reactive to a self-peptide (FL9) bound to mouse MHC-E (Qa-1b) that is presented in response to loss of the MHC I processing enzyme ERAAP, termed QFL T cells. We find that mature QFL thymocytes are predominantly CD8{beta}+CD4-, show signs of agonist selection, and give rise to both CD8 and CD8{beta} intraepithelial lymphocytes (IEL), as well as memory phenotype CD8{beta} T cells. QFL T cells require the MHC I subunit {beta}-2 microglobulin ({beta}2m), but do not require Qa1b or classical MHC I for positive selection. However, QFL thymocytes do require Qa1b for agonist selection and full functionality. Our data highlight the relaxed requirements for positive selection of an MHC-E restricted T cell population and suggest a CD8{beta}+CD4-pathway for development of CD8 IELs.

immunology↗

bioRxiv2022

Murine cytomegalovirus downregulates ERAAP and induces an unconventional T cell response to self

The endoplasmic reticulum aminopeptidase associated with antigen presentation (ERAAP) plays a crucial role in shaping the peptide-MHC I repertoire and maintaining immune surveillance. While murine cytomegalovirus (MCMV) has multiple strategies for manipulating the antigen processing pathway to evade immune responses, the host has also developed ways to counter viral immune evasion. In this study, we found that MCMV modulates ERAAP and induces an IFN-{gamma} producing CD8+ T cell effector response that targets uninfected ERAAP deficient cells. We also observed that ERAAP downregulation during infection led to presentation of the self-peptide FL9 on non-classical Qa-1b, thereby eliciting Qa-1b restricted QFL T cells to proliferate in the liver and spleen of infected mice. QFL T cells upregulated effector markers upon MCMV infection and were sufficient to reduce viral load after transfer to immunodeficient mice. Our study highlights the consequences of ERAAP dysfunction during viral infection and provides potential targets for antiviral therapies.

immunology↗