Sian Llewellyn‐Lacey
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- CAR-T cell therapy research
- HIV Research and Treatment
- Cytomegalovirus and herpesvirus research
- Diabetes and associated disorders
- vaccines and immunoinformatics approaches
- Long-Term Effects of COVID-19
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Hepatitis C virus research
- Renal and related cancers
- Hepatitis B Virus Studies
- Herpesvirus Infections and Treatments
- IL-33, ST2, and ILC Pathways
- Hepatitis Viruses Studies and Epidemiology
- Liver Diseases and Immunity
- Endoplasmic Reticulum Stress and Disease
- Dermatological and COVID-19 studies
- Macrophage Migration Inhibitory Factor
- Poxvirus research and outbreaks
- HIV/AIDS Research and Interventions
Cardiff University
2016-2025
University Hospital of Wales
2020-2025
Sapporo Medical University
2019
National Institute of Allergy and Infectious Diseases
2018
Institute of Infection and Immunity
2014
Tenovus Cancer Care
2005-2008
The T cell receptor (TCR) orchestrates immune responses by binding to foreign peptides presented at the surface in context of major histocompatibility complex (MHC) molecules. Effective immunity requires that all possible peptide-MHC molecules are recognized or risks leaving holes coverage pathogens could quickly evolve exploit. It is unclear how a limited pool <108 human TCRs can successfully provide vast array different be produced from 20 proteogenic amino acids and self-MHC (>1015...
ABSTRACT SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We systematically mapped the functional and phenotypic landscape of cell responses in a large cohort unexposed individuals as well exposed family members with acute or convalescent Acute phase displayed highly activated cytotoxic phenotype that correlated various clinical markers disease severity, whereas were polyfunctional stem-like phenotype. Importantly, detectable...
The transcription factor TOX is not exclusively linked to T cell exhaustion (see related Focus by Utzschneider and Kallies).
Objective A hallmark of chronic HBV (cHBV) infection is the presence impaired HBV-specific CD8+ T cell responses. Functional exhaustion induced by persistent antigen stimulation considered a major mechanism underlying this impairment. However, due to their low frequencies in infection, it currently unknown whether cells targeting different epitopes are similarly and share molecular profiles indicative exhaustion. Design By applying peptide-loaded MHC I tetramer-based enrichment, we could...
Tissue-resident memory CD8 + T cells in unexposed oropharyngeal lymphoid tissue exhibit specificity for SARS-CoV-2.
Mpox represents a persistent health concern with varying disease severity. Reinfections mpox virus (MPXV) are rare, possibly indicating effective memory responses to MPXV or related poxviruses, notably vaccinia (VACV) from smallpox vaccination. We assessed cross-reactive and virus-specific CD4
Hepatitis B virus (HBV)-specific CD8
Objective Chronic hepatitis B virus (HBV) infection is characterised by HBV-specific CD8+ T cell dysfunction that has been linked to Tcell exhaustion, a distinct differentiation programme associated with persisting antigen recognition. Recently, Thymocyte Selection-Associated High Mobility Group Box (TOX) was identified as master regulator of exhaustion. Here, we addressed the role TOX in different clinical phases infection. Design We investigated expression cells from 53 HLA-A*01:01,...
T cells are critical for immune protection against severe COVID-19, but it has remained unclear whether repeated exposure to SARS-CoV-2 antigens delivered in the context of vaccination fuels cell exhaustion or reshapes functionality. Here, we sampled convalescent donors with a history mild COVID-19 before and after profile functional spectrum hybrid immunity. Using combined single-cell technologies high-dimensional flow cytometry, found that frequencies capabilities spike-specific CD4
HLA-B*57 control of HIV involves enhanced CD8+ T cell responses against infected cells, but extensive heterogeneity exists in the level among B*57+ individuals. Using whole-genome sequencing untreated HIV-1-infected controllers and noncontrollers, we identified a single variant (rs643347A/G) encoding an isoleucine-to-valine substitution at position 47 (I47V) inhibitory killer immunoglobulin-like receptor KIR3DL1 as only significant modifier B*57 protection. The association was replicated...
Aging is associated with functional deficits in the naive T cell compartment, which compromise generation of de novo immune responses against previously unencountered Ags. The mechanisms that underlie this phenomenon have nonetheless remained unclear. We found CD8+ cells elderly humans were prone to apoptosis and proliferated suboptimally response stimulation via TCR. These abnormalities dysregulated lipid metabolism under homeostatic conditions enhanced levels basal activation. Importantly,...
Exhausted T cells with limited effector function are enriched in chronic hepatitis B and C virus (HBV HCV) infection. Metabolic regulation contributes to exhaustion, but it remains unclear how metabolism relates different exhaustion states, is impacted by antiviral therapy, if metabolic checkpoints regulate dysfunction.Metabolic state, transcriptome of virus-specific CD8+ from HBV-infected (n=31) HCV-infected patients (n=52) were determined ex vivo during direct-acting (DAA) therapy. flux...