Comparative Analysis of B-Cell Receptor Repertoires Induced by Live Yellow Fever Vaccine in Young and Middle-Age Donors

Age-related changes can significantly alter the state of adaptive immune system and often lead to attenuated response to novel pathogens and vaccination. In present study we employed 5′RACE UMI-based full length and nearly error-free immunoglobulin profiling to compare plasma cell antibody repertoires in young (19–26 years) and middle-age (45–58 years) individuals vaccinated with a live yellow fever vaccine, modeling a newly encountered pathogen. Our analysis has revealed age-related differences in the responding antibody repertoire ranging from distinct IGH CDR3 repertoire properties to differences in somatic hypermutation intensity and efficiency and antibody lineage tree structure. Overall, our findings suggest that younger individuals respond with a more diverse antibody repertoire and employ a more efficient somatic hypermutation process than elder individuals in response to a newly encountered pathogen

Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance

γδ T cells are considered to be innate-like lymphocytes that respond rapidly to stress without clonal selection and differentiation. Here we use next-generation sequencing to probe how this paradigm relates to human Vδ2neg T cells, implicated in responses to viral infection and cancer. The prevalent Vδ1 T cell receptor (TCR) repertoire is private and initially unfocused in cord blood, typically becoming strongly focused on a few high-frequency clonotypes by adulthood. Clonal expansions have differentiated from a naive to effector phenotype associated with CD27 downregulation, retaining proliferative capacity and TCR sensitivity, displaying increased cytotoxic markers and altered homing capabilities, and remaining relatively stable over time. Contrastingly, Vδ2+ T cells express semi-invariant TCRs, which are present at birth and shared between individuals. Human Vδ1+ T cells have therefore evolved a distinct biology from the Vδ2+ subset, involving a central, personalized role for the γδ TCR in directing a highly adaptive yet unconventional form of immune surveillance

The human Vδ2⁺ T-cell compartment comprises distinct innate-like Vγ9⁺ and adaptive Vγ9^- subsets

Vδ2+ T cells form the predominant human γδ T-cell population in peripheral blood and mediate T-cell receptor (TCR)-dependent anti-microbial and anti-Tumour immunity. Here we show that the Vδ2+ compartment comprises both innate-like and adaptive subsets. Vγ9+ Vδ2+ T cells display semi-invariant TCR repertoires, featuring public Vγ9 TCR sequences equivalent in cord and adult blood. By contrast, we also identify a separate, Vγ9- Vδ2+ T-cell subset that typically has a CD27hiCCR7+CD28+IL-7Rα+ naive-like phenotype and a diverse TCR repertoire, however in response to viral infection, undergoes clonal expansion and differentiation to a CD27loCD45RA+CX3CR1+granzymeA/B+ effector phenotype. Consistent with a function in solid tissue immunosurveillance, we detect human intrahepatic Vγ9- Vδ2+ T cells featuring dominant clonal expansions and an effector phenotype. These findings redefine human γδ T-cell subsets by delineating the Vδ2+ T-cell compartment into innate-like (Vγ9+) and adaptive (Vγ9-) subsets, which have distinct functions in microbial immunosurveillance

Origin and Ion Charge State Evolution of Solar Wind Transients during 4 – 7 August 2011

We present a study of the complex event consisting of several solar wind transients detected by the Advanced Composition Explorer (ACE) on 4 – 7 August 2011, which caused a geomagnetic storm with Dst=−110nT. The supposed coronal sources, three flares and coronal mass ejections (CMEs), occurred on 2 – 4 August 2011 in active region (AR) 11261. To investigate the solar origin and formation of these transients, we study the kinematic and thermodynamic properties of the expanding coronal structures using the Solar Dynamics Observatory/Atmospheric Imaging Assembly (SDO/AIA) EUV images and differential emission measure (DEM) diagnostics. The Helioseismic and Magnetic Imager (HMI) magnetic field maps were used as the input data for the 3D magnetohydrodynamic (MHD) model to describe the flux rope ejection (Pagano, Mackay, and Poedts, 2013b). We characterize the early phase of the flux rope ejection in the corona, where the usual three-component CME structure formed. The flux rope was ejected with a speed of about 200kms−1 to the height of 0.25R⊙. The kinematics of the modeled CME front agrees well with the Solar Terrestrial Relations Observatory (STEREO) EUV measurements. Using the results of the plasma diagnostics and MHD modeling, we calculate the ion charge ratios of carbon and oxygen as well as the mean charge state of iron ions of the 2 August 2011 CME, taking into account the processes of heating, cooling, expansion, ionization, and recombination of the moving plasma in the corona up to the frozen-in region. We estimate a probable heating rate of the CME plasma in the low corona by matching the calculated ion composition parameters of the CME with those measured in situ for the solar wind transients. We also consider the similarities and discrepancies between the results of the MHD simulation and the observations

MAGERI: Computational pipeline for molecular-barcoded targeted resequencing

<div><p>Unique molecular identifiers (UMIs) show outstanding performance in targeted high-throughput resequencing, being the most promising approach for the accurate identification of rare variants in complex DNA samples. This approach has application in multiple areas, including cancer diagnostics, thus demanding dedicated software and algorithms. Here we introduce MAGERI, a computational pipeline that efficiently handles all caveats of UMI-based analysis to obtain high-fidelity mutation profiles and call ultra-rare variants. Using an extensive set of benchmark datasets including gold-standard biological samples with known variant frequencies, cell-free DNA from tumor patient blood samples and publicly available UMI-encoded datasets we demonstrate that our method is both robust and efficient in calling rare variants. The versatility of our software is supported by accurate results obtained for both tumor DNA and viral RNA samples in datasets prepared using three different UMI-based protocols.</p></div