A5009573818- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Drug-Induced Adverse Reactions
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Reproductive System and Pregnancy
- Urticaria and Related Conditions
- Autoimmune Bullous Skin Diseases
- Influenza Virus Research Studies
- Reproductive Physiology in Livestock
- Immune responses and vaccinations
- Phagocytosis and Immune Regulation
- vaccines and immunoinformatics approaches
- Asthma and respiratory diseases
- Education and Social Development in Ukraine
- Celiac Disease Research and Management
- Advanced Biosensing Techniques and Applications
- Gender Roles and Identity Studies
- Microscopic Colitis
- Galectins and Cancer Biology
- Silicone and Siloxane Chemistry
- Immune Response and Inflammation
- Signaling Pathways in Disease
Peter Doherty Institute
2013-2022
The University of Melbourne
2011-2022
Monash University
2004-2005
Russian Academy of Sciences
1988
Mucosal-associated invariant T cells (MAIT cells) express a semi-invariant cell receptor (TCR) α-chain, TRAV1-2–TRAJ33, and are activated by vitamin B metabolites bound the major histocompatibility complex (MHC)–related class I–like molecule, MR1. Understanding MAIT biology has been restrained lack of reagents to specifically identify characterize these cells. Furthermore, use surrogate markers may misrepresent population. We show that modified human MR1 tetramers loaded with potent 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...
Mucosal associated invariant T (MAIT) cells recognise conserved microbial metabolites from riboflavin synthesis. Striking evolutionary conservation and pulmonary abundance implicate them in antibacterial host defence, yet their functions protection against clinically important pathogens are unknown. Here we show that mouse Legionella longbeachae infection induces MR1-dependent MAIT cell activation rapid accumulation of with immune detectable immunocompetent animals. is more evident mice...
Mucosal-associated invariant T (MAIT) cells are MR1-restricted innate-like conserved across mammalian species, including mice and humans. By sequencing RNA from sorted MR1-5-OP-RU tetramer+ derived either human blood or murine lungs, we define the basic transcriptome of an activated MAIT cell in both species demonstrate how this profile changes during resolution infection reinfection. We observe strong similarities between humans mice. In activation leads to expression pro-inflammatory...
Mucosal associated invariant T (MAIT) cells are evolutionarily-conserved, innate-like lymphocytes which abundant in human lungs and can contribute to protection against pulmonary bacterial infection. MAIT also activated during viral infections, yet it remains unknown whether play a significant protective or even detrimental role infections vivo. Using murine experimental challenge with two strains of influenza A virus, we show that accumulate early infection, upregulation CD25, CD69 Granzyme...
Mucosal-associated invariant T (MAIT) cells express a semiinvariant αβ cell receptor (TCR) that binds MHC class I-like molecule (MR1). However, the molecular basis for MAIT TCR recognition by MR1 is unknown. In this study, we present crystal structure of human Vα7.2Jα33-Vβ2 TCR. Mutagenesis revealed highly conserved requirements TCR-MR1 interaction across different TCRs stimulated distinct microbial sources. Individual residues within β chain were dispensable with MR1, whereas α controlled...
ICOS- and IL-23–mediated costimulation are important for driving in vivo activation of antigen-specific MAIT cells.
The CD3εγ heterodimer is essential for expression and function of the T cell receptor. crystal structure human described to 2.1-Å resolution complexed with OKT3, a therapeutic mAb that not only activates tolerizes mature cells but also induces regulatory cells. mode dimerization provides general structural basis CD3 assembly maps candidate antigen receptor docking sites, including duplicated linear region rich in acidic residues unique CD3ε. OKT3 binds an atypically small area CD3ε has low...
HLA-G is a nonclassical major histocompatibility complex class I (MHC-I) molecule that primarily expressed at the fetal–maternal interface, where it thought to play role in protecting fetus from maternal immune response. binds limited repertoire of peptides and interacts with inhibitory leukocyte Ig-like receptors LIR-1 LIR-2 possibly certain natural killer cell receptors. To gain further insights into function, we determined 1.9-Å structure monomeric complexed endogenous peptide ligand...
αβ T cell receptors (TCRs) are genetically restricted to corecognize peptide antigens bound self-major histocompatibility complex (pMHC) molecules; however, the basis for this MHC specificity remains unclear. Despite current dogma, evaluation of TCR–pMHC-I structural database shows that nongermline-encoded complementarity-determining region (CDR)-3 loops often contact MHC-I, and germline-encoded CDR1 -2 frequently participate in peptide-mediated interactions. Nevertheless, different TCRs...
Mucosal-associated invariant T (MAIT) cells detect microbial infection via recognition of riboflavin-based antigens presented by the major histocompatibility complex class I (MHC-I)–related protein 1 (MR1). Most MAIT in human peripheral blood express CD8αα or CD8αβ coreceptors, and binding site for CD8 on MHC-I molecules is relatively conserved MR1. Yet, there no direct evidence interacting with MR1 functional consequences thereof. Similarly, role lymphocyte function remains ill-defined....
Little is known regarding the basis for selection of semi-invariant αβ T cell receptor (TCR) expressed by natural killer (NKT) cells or how this mediates recognition CD1d–glycolipid complexes. We have determined structures two human NKT TCRs that differ in their CDR3β composition and length. Both contain a conserved, positively charged pocket at ligand interface lined residues from invariant TCR α- β-chains. The cavity centrally located ideally suited to interact with exposed glycosyl head...
Current views emphasize TCR diversity as a key feature that differentiates the group 1 (CD1a, CD1b, CD1c) and 2 (CD1d) CD1 systems. Whereas sequence motifs define CD1d-reactive NKT cells, available data do not allow TCR-based organization of repertoire. The observed might result from donor-to-donor differences in repertoire, seen for MHC-restricted T cells. Alternatively, differing isoforms, Ags, methods used to identify TCRs. Using CD1b tetramers isolate clones recognizing same glycolipid,...
Abstract Mucosal-associated invariant T (MAIT) cells produce inflammatory cytokines and cytotoxic granzymes in response to by-products of microbial riboflavin synthesis. Although MAIT are protective against some pathogens, we reasoned that they might contribute pathology chronic bacterial infection. We observed proximity Helicobacter pylori bacteria human gastric tissue, so, using MR1-tetramers, examined whether gastritis a mouse H. SS1 infection model. Following infection, accumulated high...
HLA‐B57 and HLA‐B58 are major histocompatibility class (MHC)‐I allotypes that potentially predictive of important clinical immune phenotypes. HLA‐B*5701 is strongly associated with hypersensitivity to the HIV drug abacavir, liver toxicity from antibiotic flucloxacillin a marker for slow progression AIDS. HLA‐B*5801 allopurinol used treat hyperuricaemia recurrent gout. Here we describe monoclonal antibody (mAb) specific provides an inexpensive sensitive screen these MHC‐I allotypes. The...
Abstract Background/Objectives Mucosal‐associated invariant T ( MAIT ) cells are a novel subset of innate‐like T‐cells that enriched in mucosal tissues. Their presence human skin has only recently been recognised. We describe the expression skin‐tropic molecules on at steady state and investigate their contribution to various dermatoses with known T‐cell involvement. Methods To examine by state, we performed flow cytometric analysis blood samples from healthy donors. any potential wider...
Multiple genetic and nongenetic factors can modify the action of a drug, resulting in varied responses to particular drug across different individuals. Personalized medicine incorporates comprehensive knowledge these facilitate selection optimal therapy, reduce adverse reactions, increase patient compliance efficiency therapy. Pharmacogenomics, which integrates an individual's make-up for diagnostic decisions or therapeutic interventions is closely linked personalized medicine, being...