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CD4 + T cells are central to adaptive immunity. Their role in cross-protection in viral infections such as influenza and severe acute respiratory syndrome (SARS) is well documented; however, molecular rules governing T cell receptor (TCR) engagement of peptide-human leukocyte antigen (pHLA) class II are less understood. Here, we exploit an aspect of HLA class II presentation, the peptide-flanking residues (PFRs), to "tune" CD4 + T cell responses within an in vivo model system of influenza. Using a recombinant virus containing targeted substitutions at immunodominant HLA-DR1 epitopes, we demonstrate limited weight loss and improved clinical scores after heterosubtypic re-challenge. We observe enhanced protection linked to lung-derived influenza-specific CD4 + and CD8 + T cells prior to re-infection. Structural analysis of the ternary TCR:pHLA complex identifies that flanking amino acids influence side chains in the core 9-mer peptide, increasing TCR affinity. Augmentation of CD4 + T cell immunity is achievable with a single mutation, representing a strategy to enhance adaptive immunity that is decoupled from vaccine modality., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Existing literature indicates that academic staff experience increasing levels of work stress. This study investigated associations between day-to-day threat and challenge appraisal and day-to-day problem-focused coping, emotion-focused coping, and seeking social support among academic office workers. This study is based on an Ecological Momentary Assessment (EMA) design with a 15-working day data collection period utilising our self-developed STRAW smartphone application. A total of 55 office workers from academic institutions in Belgium (n = 29) and Slovenia (n = 26) were included and 3665 item measurements were analysed. Participants were asked approximately every 90 min about their appraisal of stressful events (experienced during the working day) and their coping styles. For data analysis, we used an unstructured covariance matrix in our linear mixed models. Challenge appraisal predicted problem-focused coping and threat appraisal predicted emotion-focused coping. Our findings suggest an association between threat appraisal as well as challenge appraisal and seeking social support. Younger and female workers chose social support more often as a coping style. While working from home, participants were less likely to seek social support. The findings of our EMA study confirm previous research on the relationship between stress appraisal and coping with stress. Participants reported seeking social support less while working from home compared to working at the office, making the work location an aspect that deserves further research., (© 2023 John Wiley & Sons Ltd.)