Date: 7 June 2024 (Friday)
Time: 5:00 pm – 6:00 pm
Venue: via ZOOM  Meeting ID 922 9782 3956    Passcode 750251

5:00 p.m.

Presenter: Yu ZHENG (PhD candidate)
Primary Supervisor: Prof. Heidi LING
Presentation Title: Develop DNA-origami based multimer (“Orimer”) to detect T cell-epitope recognition
Abstract: The recognition between T cell receptor (TCR) and antigenic peptide-MHC (pMHC) is an important initiative event, triggering subsequent T cell activation. Identifying specificity of TCR provides information of which epitope arouses robust T cell response, and can be applied to aspects such as vaccine candidate selection. Conventional detection uses pMHC tetramer as platform, yet could omit some positive signals, as its binding affinity threshold is higher than some low-affinity TCR-pMHC activations. Here we develop “Orimer”, a novel platform based on DNA-origami technology, with higher avidity and enhanced staining sensitivity, showing more low-affinity TCR-antigen interactions successfully detected. OVA antigen variants and OT1 TCR pair is selected as proof of principle. Overall, we aim to profile TCR-pMHC interaction more comprehensively, with fewer biologically significant interactions being missed. This will help under many disease settings, such as investigation of low-affinity autoimmune epitope recognition and therapy design.

5:30 p.m.

Presenter: Wenjing LAI (PhD candidate)
Primary Supervisor: Prof. Heidi LING
Presentation Title: Genome-wide identification of mutations in influenza A virus that enhance T cell response
Abstract: Major Histocompatibility Complex (MHC) regulates T cell activation through antigen presentation and affects T cell cytotoxicity. Previous research has elucidated the mechanisms of HIV and herpes viruses escaping immune surveillance by impairing MHC class I or class II mediated viral antigen presentation^1,2. Recent studies have reported the down-regulation of MHC class I induced by influenza A and influenza B viruses, while the mechanisms remain controversial³. Therefore, it is important to dissect the viral factors responsible for down-regulation of MHC class I expression. In this research, we construct an influenza viral mutant library at single amino acid resolution and use fluorescence-activated cell sorting (FACS) to screen for mutations that can up-regulate MHC class I presentation on a high-throughput scale. We aim to disable the viral MHC down-regulation function for potential vaccine design and cancer immunotherapy. The targets of T cell response elicited by our vaccination strategy are conserved. Such vaccine will have broader protection compared to the current antibody-based vaccines.

References:

1. Dirk, B. S., Pawlak, E. N., Johnson, A. L., Van Nynatten, L. R., Jacob, R. A., Heit, B., & Dikeakos, J. D. (2016). HIV-1 Nef sequesters MHC-I intracellularly by targeting early stages of endocytosis and recycling. Scientific reports, 6(1), 37021.
2. Orr, M. T., Edelmann, K. H., Vieira, J., Corey, L., Raulet, D. H., & Wilson, C. B. (2005). Inhibition of MHC class I is a virulence factor in herpes simplex virus infection of mice. PLoS pathogens, 1(1), e7. https://doi.org/10.1371/journal.ppat.0010007
3. Koutsakos, M., McWilliam, H. E. G., Aktepe, T. E., Fritzlar, S., Illing, P. T., Mifsud, N. A., Purcell, A. W., Rockman, S., Reading, P. C., Vivian, J. P., Rossjohn, J., Brooks, A. G., Mackenzie, J. M., Mintern, J. D., Villadangos, J. A., Nguyen, T. H. O., & Kedzierska, K. (2019). Downregulation of MHC Class I Expression by Influenza A and B Viruses. Frontiers in immunology, 10, 1158. https://doi.org/10.3389/fimmu.2019.01158

ALL ARE WELCOME

Should you have any enquiries, please feel free to contact Jerry Siu at 3917 6912.