About

Ellen Robey is a Professor of Immunology and Pathogenesis within the Department of Molecular & Cell Biology at the University of California, Berkeley. She is associated with the Center for Computational Biology and serves as an associated faculty member. Her contact email is erobey@berkeley.edu. Further details about her research focus, background, and key contributions are not provided in the available page text.

Research topics

• Biology
• Immunology
• Genetics
• Virology
• Cell biology

Selected publications

• Author response for "Non-cognate CD8 Binding to MHC I Promotes Positive Selection of an MHC-E Restricted CD8 T cell Population"

  2026-02-18

  peer-review
  PublisherDOI

• Non‐cognate CD8 Binding to MHC I Promotes Positive Selection of an MHC‐E Restricted CD8 T Cell Population

  European Journal of Immunology · 2026-03-01

  articleOpen accessCorresponding

  ABSTRACT MHC‐E‐restricted CD8 T cells are emerging as an attractive therapeutic mechanism due to their strong protective capacity and ability to respond to cells with defects in antigen processing; however, their thymic development remains poorly understood. Here, we explore the MHC ligand requirement for thymic development of T cells reactive to a self‐peptide (FL9) presented by mouse MHC‐E (Qa1 b ) under conditions of deficiency in the endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP), called QFL T cells. We show that, while QFL T cells can develop in the absence of the restricting Qa1 b molecule, their development was abrogated in the combined absence of classical MHC Ia and Qa1 b . Interestingly, QFL thymocytes did not recognize classical MHC Ia molecules through their TCR but instead used non‐cognate CD8‐MHC Ia interactions to boost responses to MHC Ib ligands. Furthermore, we also identify an alternative ligand for the QFL TCR, the MHC Ib molecule H2‐T11. Our data provide evidence that both cognate and non‐cognate MHC interactions contribute to the development of a Qa1 b ‐specific T cell population.

  PublisherDOI

• Author response for "Non-cognate CD8 Binding to MHC I Promotes Positive Selection of an MHC-E Restricted CD8 T cell Population"

  2026-01-12

  peer-review
  PublisherDOI

• Age-related remodeling of the sialoglycans dampens murine CD8 ⁺ T cell function

  Science Advances · 2025-09-26 · 2 citations

  articleOpen access

  Glycans regulate cellular function, yet how aging affects the glycocalyx remains unclear. Here, we investigate changes in immune cell glycocalyx with age and find that α2,6-linked sialic acid, a glycan epitope associated with inhibitory signaling, is down-regulated in T cells from old animals. This reduction is tightly correlated with age-associated accumulation of effector T cells, which have little to no α2,6-linked sialic acid. To understand how α2,6-linked sialic acid affects T cell physiology, we generated a mouse model with T cell–specific deletion of sialyltransferase gene St6gal1 . The lack of α2,6-linked sialic acid leads to reduced responsiveness in naïve T cells, leading to impaired T cell responses against Listeria monocytogenes infection and tumor growth. PD-1 pathway blockade partially restores St6gal1 -deficient T cells’ ability to control tumor growth. These findings suggest that α2,6-linked sialic acid is critical for maintaining long-term T cell responsiveness, and its loss may contribute to decreased T cell function with age.

  PublisherDOI

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

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-06

  preprintOpen accessSenior authorCorresponding

  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 TCRα 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.

  PublisherOA PDFDOI

• Adjusting to self in the thymus: CD4 versus CD8 lineage commitment and regulatory T cell development

  The Journal of Experimental Medicine · 2024-07-09 · 17 citations

  reviewOpen accessSenior author

  During thymic development, thymocytes adjust their TCR response based on the strength of their reactivity to self-peptide MHC complexes. This tuning process allows thymocytes with a range of self-reactivities to survive positive selection and contribute to a diverse T cell pool. In this review, we will discuss recent advances in our understanding of how thymocytes tune their responsiveness during positive selection, and we present a "sequential selection" model to explain how MHC specificity influences lineage choice. We also discuss recent evidence for cell type diversity in the medulla and discuss how this heterogeneity may contribute to medullary niches for negative selection and regulatory T cell development.

  PublisherOA PDFDOI

• Fam49b dampens TCR signal strength to regulate survival of positively selected thymocytes and peripheral T cells

  eLife · 2024-07-17 · 2 citations

  articleOpen access

  The fate of developing T cells is determined by the strength of T cell receptor (TCR) signal they receive in the thymus. This process is finely regulated through the tuning of positive and negative regulators in thymocytes. The Family with sequence similarity 49 member B (Fam49b) protein is a newly discovered negative regulator of TCR signaling that has been shown to suppress Rac-1 activity in vitro in cultured T cell lines. However, the contribution of Fam49b to the thymic development of T cells is unknown. To investigate this important issue, we generated a novel mouse line deficient in Fam49b (Fam49b-KO). We observed that Fam49b-KO double positive (DP) thymocytes underwent excessive negative selection, whereas the positive selection stage was unaffected. Fam49b deficiency impaired the survival of single positive thymocytes and peripheral T cells. This altered development process resulted in significant reductions in CD4 and CD8 single-positive thymocytes as well as peripheral T cells. Interestingly, a large proportion of the TCRγδ + and CD8αα + TCRαβ + gut intraepithelial T lymphocytes were absent in Fam49b-KO mice. Our results demonstrate that Fam49b dampens thymocytes TCR signaling in order to escape negative selection during development, uncovering the function of Fam49b as a critical regulator of the selection process to ensure normal thymocyte development and peripheral T cells survival.

  PublisherDOI

• Age-related remodeling of the glycocalyx drives T cell exhaustion

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-12-09 · 1 citations

  preprintOpen access

  Abstract Cell surface glycans, termed the glycocalyx, are essential regulators of cellular signaling and thus cellular development and functions, but how aging impacts the glycocalyx remains poorly understood. Here, using immune cells as a model system for studying the relationship between aging and glycocalyx remodeling, we show that α2,6-linked sialic acid – a terminal glycan epitope typically associated with inhibitory signaling – becomes downregulated in T cells from older animals. This downregulation is tightly correlated with age-associated accumulation of effector T cells, which are decorated with little to no α2,6-linked sialic acids. T cell aging renders older individuals more vulnerable to infections and cancers. To understand the role of α2,6-linked sialic acids in T cell physiology, we generated a mouse model with T cell-specific deletion of the sialyltransferase gene St6gal1 . The chronic depletion of α2,6-linked sialic acids led to naïve T (T N ) cells expansion in the periphery and premature T cell exhaustion. As a result, these mice were less able to control acute Listeria infection and chronic tumor growth. Blockade of the PD-1 pathway can partially restore the ability of St6gal1 -deficient T cells to control tumor growth. Together, these data suggest that α2,6-linked sialic acids are critical for maintaining long-term T cell responsiveness, and the loss of α2,6-linked sialic acids may directly contribute to age-related T cell exhaustion.

  PublisherOA PDFDOI

• The CD4 Versus CD8 T Cell Fate Decision: A Multiomics-Informed Perspective

  Annual Review of Immunology · 2024-01-25 · 23 citations

  reviewOpen accessSenior author

  The choice of developing thymocytes to become CD8+ cytotoxic or CD4+ helper T cells has been intensely studied, but many of the underlying mechanisms remain to be elucidated. Recent multiomics approaches have provided much higher resolution analysis of gene expression in developing thymocytes than was previously achievable, thereby offering a fresh perspective on this question. Focusing on our recent studies using CITE-seq (cellular indexing of transcriptomes and epitopes) analyses of mouse thymocytes, we present a detailed timeline of RNA and protein expression changes during CD8 versus CD4 T cell differentiation. We also revisit our current understanding of the links between T cell receptor signaling and expression of the lineage-defining transcription factors ThPOK and RUNX3. Finally, we propose a sequential selection model to explain the tight linkage between MHC-I versus MHC-II recognition and T cell lineage choice. This model incorporates key aspects of previously proposed kinetic signaling, instructive, and stochastic/selection models.

  PublisherDOI

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

  Frontiers in Immunology · 2023-10-31 · 5 citations

  articleOpen accessSenior authorCorresponding

  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-1 b ) 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 CD8αβ+CD4-, show signs of agonist selection, and give rise to both CD8αα and CD8αβ intraepithelial lymphocytes (IEL), as well as memory phenotype CD8αβ T cells. QFL T cells require the MHC I subunit β-2 microglobulin (β2m), but do not require Qa1 b or classical MHC I for positive selection. However, QFL thymocytes do require Qa1 b 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 CD8αβ+CD4- pathway for development of CD8αα IELs.

  PublisherOA PDFDOI

Recent grants

• Visualizing of Immune Responses to Toxoplasma Gondii

  NIH · $4.8M · 2005–2020

• NIH Grant P01AI065831

  NIH · $16.0M · 2012

• Regulation of T cell responses during chronic infection by Toxoplasma gondii

  NIH · $192k · 2011–2016

• NIH Grant S10RR026821

  NIH · $472k · 2012

• Immunology & Molecular Medicine Program Training Grant

  NIH · $4.2M · 2012–2029

Frequent coauthors

• Chan‐Su Park

  75 shared

• Jian Guan

  Peking University

  74 shared

• Scheherazade Sadegh‐Nasseri

  Johns Hopkins Medicine

  70 shared

• J. David Peske

  66 shared

• Michael Manoharan Valerio

  University of California, Berkeley

  64 shared

• Nilabh Shastri

  Johns Hopkins Medicine

  33 shared

• Seong‐Ji Han

  National Institutes of Health

  32 shared

• Dragana Cado

  University of California, Berkeley

  32 shared

Labs

• Center for Computational BiologyPI