MHC-related protein 1-restricted recognition of cancer via a semi-invariant TCR-α chain.

The T cell antigen presentation platform MR1 consists of 6 allomorphs in humans that differ by no more than 5 amino acids. The principal function of this highly conserved molecule involves presenting microbial metabolites to the abundant mucosal-associated invariant T (MAIT) cell subset. Recent developments suggest that the role of MR1 extends to presenting antigens from cancer cells, a function dependent on the K43 residue in the MR1 antigen binding cleft.

HLA A*24:02-restricted T cell receptors cross-recognize bacterial and preproinsulin peptides in type 1 diabetes.

CD8+ T cells destroy insulin-producing pancreatic β cells in type 1 diabetes through HLA class I-restricted presentation of self-antigens. Combinatorial peptide library screening was used to produce a preferred peptide recognition landscape for a patient-derived T cell receptor (TCR) that recognized the preproinsulin-derived (PPI-derived) peptide sequence LWMRLLPLL in the context of disease risk allele HLA A*24:02. Data were used to generate a strong superagonist peptide, enabling production of an autoimmune HLA A*24:02-peptide-TCR structure by crystal seeding.

A targeted single mutation in influenza A virus universal epitope transforms immunogenicity and protective immunity via CD4 T cell activation.

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.

Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope.

We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A02. The Spike P272L mutation that has arisen in at least 112 different SARS-CoV-2 lineages to date, including in lineages classified as "variants of concern," was not recognized by the large CD8 T cell response seen across cohorts of HLA A02 convalescent patients and individuals vaccinated against SARS-CoV-2, despite these responses comprising of over 175 different individual T cell receptors. Viral escape at prevalent T cell epitopes restricted by high frequency HLAs may be particularly problematic when vaccine immunity is focused on a single protein such as SARS-CoV-2 Spike, providing a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlighting the need for monitoring T cell escape in new SARS-CoV-2 variants.

Bridge to the future: Important lessons from 20 years of ecosystem observations made by the OzFlux network.

In 2020, the Australian and New Zealand flux research and monitoring network, OzFlux, celebrated its 20 anniversary by reflecting on the lessons learned through two decades of ecosystem studies on global change biology. OzFlux is a network not only for ecosystem researchers, but also for those 'next users' of the knowledge, information and data that such networks provide. Here, we focus on eight lessons across topics of climate change and variability, disturbance and resilience, drought and heat stress and synergies with remote sensing and modelling.

Large differences in CO emissions from two dairy farms on a drained peatland driven by contrasting respiration rates during seasonal dry conditions.

Drained peatlands are major sources of CO to the atmosphere, yet the effects of land management and hydrological extremes have been little-studied at spatial scales relevant to agricultural enterprises. We measured fluxes of CO using the eddy covariance (EC) technique at two adjacent dairy farms on a drained peatland in Aotearoa New Zealand with remaining peat depths 5.5-8 m.

CD4 T Cells Recognize Conserved Influenza A Epitopes through Shared Patterns of V-Gene Usage and Complementary Biochemical Features.

T cell recognition of peptides presented by human leukocyte antigens (HLAs) is mediated by the highly variable T cell receptor (TCR). Despite this built-in TCR variability, individuals can mount immune responses against viral epitopes by using identical or highly related TCRs expressed on CD8 T cells. Characterization of these TCRs has extended our understanding of the molecular mechanisms that govern the recognition of peptide-HLA.

GPU-Accelerated Discovery of Pathogen-Derived Molecular Mimics of a T-Cell Insulin Epitope.

The strong links between (Human Leukocyte Antigen) HLA, infection and autoimmunity combine to implicate T-cells as primary triggers of autoimmune disease (AD). T-cell crossreactivity between microbially-derived peptides and self-peptides has been shown to break tolerance and trigger AD in experimental animal models. Detailed examination of the potential for T-cell crossreactivity to trigger human AD will require means of predicting which peptides might be recognised by autoimmune T-cell receptors (TCRs).

Recovery of the CO sink in a remnant peatland following water table lowering.

Peatland biological, physical and chemical properties change over time in response to alterations in long-term water table position. Such changes complicate our ability to predict the response of peatland carbon stocks to sustained drying. In order to better understand the effect of sustained lowering of the water table on peatland carbon dynamics, we re-visited a drainage-affected bog, repeating eddy covariance measurements of CO flux after a 16-year interval.

Peptide Super-Agonist Enhances T-Cell Responses to Melanoma.

Recent immunotherapeutic approaches using adoptive cell therapy, or checkpoint blockade, have demonstrated the powerful anti-cancer potential of CD8 cytotoxic T-lymphocytes (CTL). While these approaches have shown great promise, they are only effective in some patients with some cancers. The potential power, and relative ease, of therapeutic vaccination against tumour associated antigens (TAA) present in different cancers has been a long sought-after approach for harnessing the discriminating sensitivity of CTL to treat cancer and has seen recent renewed interest following cancer vaccination successes using unique tumour neoantigens.

Water table fluctuations control CO exchange in wet and dry bogs through different mechanisms.

High water tables (WT) stabilise peatland carbon (C) through regulation of biogeochemical processes. The impact of peatland WT on ecosystem function, including C exchange, alters over time, and the factors that cause some peatlands to display resilience and others to undergo degradation are poorly understood. Here we use CO flux measurements, measured by eddy covariance, to compare ecosystem function between two raised bogs; one drainage-affected, with a deep and fluctuating water table and the other near-natural, with a shallow and stable water table.

Optimized Peptide-MHC Multimer Protocols for Detection and Isolation of Autoimmune T-Cells.

Peptide-MHC (pMHC) multimers have become the "gold standard" for the detection and isolation of antigen-specific T-cells but recent evidence shows that normal use of these reagents can miss fully functional T-cells that bear T-cell receptors (TCRs) with low affinity for cognate antigen. This issue is particularly pronounced for anticancer and autoimmune T-cells as self-reactive T-cell populations are enriched for low-affinity TCRs due to the removal of cells with higher affinity receptors by immune tolerance mechanisms. Here, we stained a wide variety of self-reactive human T-cells using regular pMHC staining and an optimized technique that included: (i) protein kinase inhibitor (PKI), to prevent TCR triggering and internalization, and (ii) anti-fluorochrome antibody, to reduce reagent dissociation during washing steps.

Thermal Stability of Heterotrimeric pMHC Proteins as Determined by Circular Dichroism Spectroscopy.

T cell receptor (TCR) recognition of foreign peptide fragments, presented by peptide major histocompatibility complex (pMHC), governs T-cell mediated protection against pathogens and cancer. Many factors govern T-cell sensitivity, including the affinity of the TCR-pMHC interaction and the stability of pMHC on the surface of antigen presenting cells. These factors are particularly relevant for the peptide vaccination field, in which more stable pMHC interactions could enable more effective protection against disease.

Structural Mechanism Underpinning Cross-reactivity of a CD8+ T-cell Clone That Recognizes a Peptide Derived from Human Telomerase Reverse Transcriptase.

T-cell cross-reactivity is essential for effective immune surveillance but has also been implicated as a pathway to autoimmunity. Previous studies have demonstrated that T-cell receptors (TCRs) that focus on a minimal motif within the peptide are able to facilitate a high level of T-cell cross-reactivity. However, the structural database shows that most TCRs exhibit less focused antigen binding involving contact with more peptide residues.

Modelling carbon and water exchange of a grazed pasture in New Zealand constrained by eddy covariance measurements.

We used two years of eddy covariance (EC) measurements collected over an intensively grazed dairy pasture to better understand the key drivers of changes in soil organic carbon stocks. Analysing grazing systems with EC measurements poses significant challenges as the respiration from grazing animals can result in large short-term CO2 fluxes. As paddocks are grazed only periodically, EC observations derive from a mosaic of paddocks with very different exchange rates.