CD8+ T cells recognising their cognate antigen are typically recruited as a polyclonal population consisting of multiple clonotypes with varying T-cell receptor (TCR) affinity to the target peptide-MHC (pMHC) complex. Advances in single-cell sequencing have increased accessibility towards identifying TCRs with matched antigens. Here we present the discovery of a monoclonal CD8+ T cell population with specificity for a hepatitis C virus (HCV)-derived HLA class I epitope (HLA-B*07:02 GPRLGVRAT) which was isolated directly ex vivo from an individual with an episode of acutely resolved HCV infection. This population was absent prior to infection and underwent expansion and stable maintenance for at least two years after infection as measured by HLA-multimer staining. Furthermore, the monoclonal clonotype was characterised by an unusually long dissociation time (half-life = 794 seconds and koff = 5.73×10-4) for its target antigen when compared to previously published results. A comparison with related populations of HCV-specific populations derived from the same individual and a second individual suggest that high-affinity TCR-pMHC interactions may be inherent to epitope identity and shape the phenotype of responses which has implications for rational TCR selection and design in the age of personalised immunotherapies.

Individuals with low socioeconomic status (SES) are at greater risk of contracting and developing severe disease compared to people with higher SES. Age, sex, host genetics, smoking, and Cytomegalovirus (CMV) serostatus are known to have a major impact on human immune responses and thus susceptibility to infection. However, the impact of SES on immune variability is not well understood or explored. Here, we used data from the Milieu Intérieur project, a study of 1,000 healthy volunteers with extensive demographic and biological data, to examine the effect of SES on immune variability. We developed an Elo-rating system using socioeconomic features such as education, income, and household to objectively rank SES in the 1,000 donors. We observed sex specific SES associations, such as females with a low SES having significantly higher frequency of CMV seropositivity compared to high SES females, and males from a low SES having significantly higher frequency of active smoking compared to high SES males. Using random forest models, we identified specific immune genes which were significantly associated with SES in both baseline and immune challenge conditions. Interestingly, many of the SES associations were sex-stimuli specific, highlighting the complexity of these interactions. Our study provides a new way of computing SES in human populations that can help identify novel SES associations and reinforces biological evidence for SES-dependent susceptibility to infection. This should serve as a basis for further understanding the molecular mechanisms behind socioeconomic status effects on immune responses and ultimately disease.

This journey traces the transition from a brief dentistry stint to a neuroimmunology exploration. The narrative unfolds through academic pursuits at the University of São Paulo, Brazil, and subsequent doctoral studies, reflecting on the initial idealism that shaped the pursuit of academia. An unexpected postdoctoral experience at the Centre de Physiopathologie de Toulouse Purpan in France introduced me to immunology, leading to an unexpected passion. Here, I explore uncertainties, decisions, and a pivotal move to Belgium, where collaboration with Adrian Liston at VIB-KU Leuven marked a maturity phase. Amid personal milestones like pregnancy and the challenges of balancing parenthood with a burgeoning career, I would like to highlight the crucial role of support systems and a thriving research environment. My journey so far culminates in the establishment of a lab, the pursuit of a permanent position, and the appointment as an assistant professor at KU Leuven.

Effective vaccines have reduced SARS-CoV-2 morbidity and mortality; however, the elderly remain the most at risk. Understanding how vaccines generate protective immunity, and how these mechanisms change with age is key for informing future vaccine design. Cytotoxic CD8+ T cells are important for killing virally infected cells, and vaccines that induce antigen specific CD8+ T cells in addition to humoral immunity provide an extra layer of immune protection. This is particularly important in cases where antibody titres are sub-optimal, as can occur in older individuals. Here, we show that in aged mice, spike-epitope specific CD8+ T cells are generated in comparable numbers to younger animals after ChAdOx1 nCoV-19 vaccination, although phenotypic differences exist. This demonstrates that ChAdOx1 nCoV-19 elicits a good CD8+ T cell response in older bodies, but that typical age-associated features are evident on these vaccine reactive T cells.