A5072318020- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Parasites and Host Interactions
- Cytomegalovirus and herpesvirus research
- Parasite Biology and Host Interactions
- Immune cells in cancer
- Helminth infection and control
- Herpesvirus Infections and Treatments
- Trace Elements in Health
- Immune Response and Inflammation
- Virus-based gene therapy research
- Aquaculture disease management and microbiota
- CAR-T cell therapy research
- Immune responses and vaccinations
- Bacterial Genetics and Biotechnology
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Parasitic Infections and Diagnostics
- Coccidia and coccidiosis research
- Bacteriophages and microbial interactions
- Plant and fungal interactions
- Cancer Research and Treatments
Peter Doherty Institute
2015-2024
The University of Melbourne
2015-2024
Moredun Research Institute
2009-2020
Australian Research Council
2013
Monash University
2011-2013
Deakin University
2002-2007
Gamma delta (γδ) T cells are essential to protective immunity. In humans, most γδ express Vγ9Vδ2+ cell receptors (TCRs) that respond phosphoantigens (pAgs) produced by cellular pathogens and overexpressed cancers. However, the molecular targets recognized these γδTCRs unknown. Here, we identify butyrophilin 2A1 (BTN2A1) as a key ligand binds Vγ9+ TCR γ chain. BTN2A1 associates with another butyrophilin, BTN3A1, act together initiate responses pAg. Furthermore, binding of second ligand,...
Mucosal-associated invariant T (MAIT) cells express an cell receptor (TCR) α-chain (TRAV1-2 joined to TRAJ33, TRAJ20, or TRAJ12 in humans), which pairs with array of TCR β-chains. MAIT TCRs can bind folate- and riboflavin-based metabolites restricted by the major histocompatibility complex (MHC)-related class I−like molecule, MR1. However, impact MR1-ligand heterogeneity on biology is unclear. We show how a previously uncharacterized MR1 ligand, acetyl-6-formylpterin (Ac-6-FP), markedly...
Tissue-resident cells exhibit tissue-specific overlays to the T RM cell residency program that includes flexible FABP isoform selection tailored tissue of lodgment.
Manipulation of the MHC-I presentation pathway, and thus limiting cell surface expression, is used by many viruses to evade immune recognition. In particular, downregulation molecules at can reduce ability CD8+ T cells recognise viral peptides presented thereby delay clearance cells. To date, influenza has not been reported. Given that virus infections are a global health concern play an important role in promoting recovery from disease, we investigated whether A B (IAV, IBV) downregulated...
A rare human allele renders MR1 unable to present microbially derived antigen, resulting in a selective loss of MAIT cells.
The antigen-presenting molecule MR1 (MHC class I-related protein 1) presents metabolite antigens derived from microbial vitamin B
The antigen-presenting molecule MR1 presents microbial metabolites related to vitamin B2 biosynthesis mucosal-associated invariant T cells (MAIT cells). Although bacteria and fungi drive the pathway, viruses have not previously been implicated in expression or its antigen presentation. We demonstrate that several herpesviruses inhibit cell surface upregulation, including a potent inhibition by herpes simplex virus type 1 (HSV-1). This profoundly suppresses targets for proteasomal...
The opportunistic human pathogen
Understanding the complex elements affecting signal resolution in cytometry is key for quality experimental design and data. In this study, we incorporate autofluorescence as a contributing factor to our understanding of corroborate its impact fluorescence detection through mathematical predictions supported by empirical evidence. Our findings illustrate critical importance extraction via full spectrum unmixing unmasking dim signals delineating expression subset distribution low abundance...
Abstract Bacterial synthesis of vitamin B2 generates a by‐product, 5‐(2‐oxopropylideneamino)‐ d ‐ribityl‐aminouracil (5‐OP‐RU), with potent immunological properties in mammals, but it is rapidly degraded water. This natural product covalently bonds to the key protein MR1 endoplasmic reticulum antigen presenting cells (APCs), enabling refolding and trafficking cell surface, where interacts T receptors (TCRs) on mucosal associated invariant lymphocytes (MAIT cells), activating their...
Abstract The MARCH E3 ubiquitin (Ub) ligase MARCH1 regulates trafficking of major histocompatibility complex class II (MHC II) and CD86, molecules critical importance to immunity. Here we show, using a genome-wide CRISPR knockout screen, that ubiquitin-like protein 3 (UBL3) is necessary component ubiquitination-mediated these in mice humans. Ubl3 -deficient have elevated MHC CD86 expression on the surface professional atypical antigen presenting cells. UBL3 also human dendritic cells (DCs)...
Novel vaccine candidates against Schistosoma japonicum are required, and antigens present in the vulnerable larval developmental stage attractive targets. Post-genomic technologies now available which can contribute to such antigen discovery. A schistosome-specific protein microarray was probed using local antibody response migrating larvae. Antigens were assessed for their novelty predicted expression host-exposed features. One further characterised its sequence structure analysed silico....
Introduction The antigen presentation molecule MHC class I related protein-1 (MR1) is best characterized by its ability to present bacterially derived metabolites of vitamin B2 biosynthesis mucosal-associated invariant T-cells (MAIT cells). Methods Through in vitro human cytomegalovirus (HCMV) infection the presence MR1 ligand we investigate modulation expression. Using coimmunoprecipitation, mass spectrometry, expression recombinant adenovirus and HCMV deletion mutants gpUS9 family members...
Asian schistosomiasis is a zoonotic parasitic disease infecting up to million people and threatening tens of millions more. Control this hindered by the animal reservoirs parasite, in particular water buffalo (Bubalus bubalis), which responsible for significant levels human transmission. A transmission-blocking vaccine administered buffaloes realistic option would aid control schistosomiasis. This will however require better understanding immunobiology naturally exposed buffaloes,...