A5035495223- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- Poxvirus research and outbreaks
- Glycosylation and Glycoproteins Research
- Viral-associated cancers and disorders
- Click Chemistry and Applications
- Advanced Proteomics Techniques and Applications
- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- CAR-T cell therapy research
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- interferon and immune responses
- Immune cells in cancer
- Immune Response and Inflammation
- Chemical Synthesis and Analysis
- Drug-Induced Adverse Reactions
- Microscopic Colitis
Monash University
2015-2025
Australian Regenerative Medicine Institute
2016-2025
Discovery Institute
2016-2024
The University of Melbourne
2010-2014
Medical Research Council
2009
Cancer Research UK
2007-2009
University of Birmingham
2007-2009
Immune Regulation (United Kingdom)
2007-2009
Abstract The role of microglia cells in Alzheimer’s disease (AD) is well recognized, however their molecular and functional diversity remain unclear. Here, we isolated amyloid plaque-containing (using labelling with methoxy-XO4, XO4 + ) non-containing (XO4 − from an AD mouse model. Transcriptomics analysis identified different transcriptional trajectories ageing mice. microglial transcriptomes demonstrated dysregulated expression genes associated late onset AD. We further showed that the...
γ1-Herpesviruses such as Epstein-Barr virus (EBV) have a unique ability to amplify loads in vivo through latent growth-transforming infection. Whether they, like α- and β-herpesviruses, been driven actively evade immune detection of replicative (lytic) infection remains moot point. We were prompted readdress this question by recent work (Pudney, V.A., A.M. Leese, A.B. Rickinson, A.D. Hislop. 2005. J. Exp. Med. 201:349–360; Ressing, M.E., S.E. Keating, D. van Leeuwen, Koppers-Lalic, I.Y....
The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. peptide repertoire is extended various posttranslational modifications, including proteasomal splicing fragments from distinct regions to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction the immunopeptidome constitutes such peptides; however, because computational limitations, not possible assess whether trans-spliced...
Current knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being fundamental importance our understanding anti-viral immunity. Here we use an advanced mass spectrometry method simultaneously quantify eight vaccinia virus peptide-MHC complexes (epitopes) on infected and amounts their source antigens at multiple times after infection. The results show a startling 1000-fold range in abundance as well strikingly different kinetics across...
CD8
The magnitude of T cell responses to infection is a function the naïve repertoire combined with context and duration antigen presentation. Using mass spectrometry, we identify quantify 21 class 1 MHC-restricted influenza A virus (IAV)-peptides following either direct or cross-presentation. All these peptides, including seven novel epitopes, elicit in infected C57BL/6 mice. Directly presented IAV epitopes maintain their relative abundance across distinct types reveal broad range epitope...
T cell epitope candidates are commonly identified using computational prediction tools in order to enable applications such as vaccine design, cancer neoantigen identification, development of diagnostics and removal unwanted immune responses against protein therapeutics. Most based on machine learning algorithms trained MHC binding or naturally processed ligand elution data. The ability currently available predict epitopes has not been comprehensively evaluated. In this study, we used a...
EBV persists for life in the human host while facing vigorous antiviral responses that are induced upon primary infection. This persistence supports idea herpesviruses have acquired dedicated functions to avoid immune elimination. The recently identified gene product BNLF2a blocks TAP. As a result, reduced amounts of peptides transported by TAP from cytoplasm into endoplasmic reticulum (ER) lumen binding newly synthesized HLA class I molecules. Thus, perturbs detection cytotoxic T cells....
Immunopeptidomics employs the use of mass spectrometry to identify and quantify peptides presented on surface cells by major histocompatibility complex (MHC; human leukocyte antigen [HLA], in humans) molecules, an essential component adaptive immunity. Currently, immunopeptidomics follows same or similar workflows as more established field shotgun proteomics, yet inherent differences between these two fields create significant drawbacks for former. In this viewpoint, we would like highlight...
Abstract Antigen recognition by CD8+ T cells is governed the pool of peptide antigens presented on cell surface in context HLA class I complexes. Studies have shown not only a high degree plasticity immunopeptidome, but also that considerable fraction all peptides generated through proteasome-mediated splicing noncontiguous regions proteins to form novel antigens. Here, we used high-resolution mass spectrometry combined with new bioinformatic approaches characterize immunopeptidome melanoma...
Neopeptide-based immunotherapy has been recognised as a promising approach for the treatment of cancers. For neopeptides to be by CD8+ T cells and induce an immune response, their binding human leukocyte antigen class I (HLA-I) molecules is necessary first step. Most epitope prediction tools thus rely on such binding. With use mass spectrometry, scale naturally presented HLA ligands that could used develop predictors expanded. However, there are rarely efforts focus integration these...
The gamma-herpesvirus Epstein-Barr virus (EBV) persists for life in infected individuals despite the presence of a strong immune response. During lytic cycle EBV many viral proteins are expressed, potentially allowing virally cells to be recognized and eliminated by CD8+ T cells. We have recently identified an evasion protein encoded EBV, BNLF2a, which is expressed early phase replication inhibits peptide- ATP-binding functions transporter associated with antigen processing. Ectopic...
Class I HLAs generally present peptides of 8-10 aa in length, although it is unclear whether peptide length preferences are affected by HLA polymorphism. In this study, we investigated the CD8(+) T cell response to BZLF1 Ag EBV, which includes overlapping sequences different size that nevertheless conform binding motif large and abundant HLA-B*44 supertype. Whereas HLA-B*18:01(+) individuals responded strongly exclusively octamer (173)SELEIKRY(180), HLA-B*44:03(+) atypically dodecamer...
Abstract We describe a cell‐free approach that employs selected reaction monitoring (SRM) in tandem mass spectrometry to identify and quantitate T‐cell epitopes. This utilises multiple epitope‐specific SRM transitions known epitopes an absolute quantitation (AQUA) peptide strategy afford AQUA. The advantage of spectrometry‐based over more traditional cell‐based assays resides the robustness transferability between laboratories ability this detect peptides simultaneously without requirement...
Type 1 diabetes is characterized by the autoimmune destruction of pancreatic β-cells. Recognition major histocompatibility complex (MHC)-bound peptides critical for both initiation and progression disease. In this study, MHC peptide complexes were purified from NIT-1 β-cells, interferon-γ (IFN-γ)-treated cells, splenic thymic tissue 12-week-old NOD mice, identified mass spectrometry. addition to global liquid chromatography-tandem spectrometry analysis, targeted approach multiple-reaction...
Abstract The major histocompatibility complex (MHC) encodes a range of immune response genes, including the human leukocyte antigens (HLAs) in humans. These molecules bind peptide and present them on cell surface for T recognition. repertoires peptides presented by HLA are termed immunopeptidomes. highly polymorphic nature genres that encode confers allotype-specific differences sequences bound ligands. Allotype-specific ligand preferences often defined peptide-binding motifs. Individuals...
Abstract The human B lymphoblastoid cell line C1R is widely regarded as leukocyte antigen‐A ( HLA ‐A)/ ‐B negative and therefore frequently exploited a recipient to study class I functions. However, the normal levels of ‐C*04:01 often hamper investigation introduced allomorphs, which particularly evident in sensitive applications such mass spectrometry. Here we describe comprehensive analysis endogenous ligands expressed on surface cells (i) define large sequence dataset ligands, (ii) refine...
The bacterial cell surface proteins intimin and invasin are virulence factors that share a common domain structure bind selectively to host receptors in the course of pathogenesis. β-barrel domains show significant sequence structural similarities. Conversely, variety with sometimes limited similarity have also been annotated as "intimin-like" "invasin" genome datasets, while other recent work on apparently unrelated virulence-associated ultimately revealed similarities invasin. Here we...