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The adaptive arm of the immune system has been suggested as an important factor in brain function. However, given the fact that interactions of neurons or glial cells with T lymphocytes rarely occur within the healthy CNS parenchyma, the underlying mechanism is still a mystery. Here we found that at the interface between the brain and blood circulation, the(More)
It is generally assumed that amino acid mutations in the surface protein, hemagglutinin (HA), of influenza viruses allow these viruses to circumvent neutralization by antibodies induced during infection. However, empirical data on circulating influenza viruses show that certain amino acid changes to HA actually increase the efficiency of neutralization of(More)
T cells play fundamental roles in adaptive immunity, relying on a diverse repertoire of T-cell receptor (TCR) α and β chains. Diversity of the TCR β chain is generated in part by a random yet intrinsically biased combinatorial rearrangement of variable (Vβ), diversity (Dβ), and joining (Jβ) gene segments. The mechanisms that determine biases in gene segment(More)
SUMMARY High-throughput sequencing provides an opportunity to analyse the repertoire of antigen-specific receptors with an unprecedented breadth and depth. However, the quantity of raw data produced by this technology requires efficient ways to categorize and store the output for subsequent analysis. To this end, we have defined a simple five-item(More)
The hemagglutination-inhibition (HI) assay is the main tool used by epidemiologists to quantify antigenic differences between circulating influenza virus strains, with the goal of selecting suitable vaccine strains. However, such quantitative measures of antigenic difference were recently shown to have poor predictive accuracy with respect to influenza(More)
The T-cell receptor (TCR) repertoire is formed by random recombinations of genomic precursor elements; the resulting combinatorial diversity renders unlikely extensive TCR sharing between individuals. Here, we studied CDR3β amino acid sequence sharing in a repertoire-wide manner, using high-throughput TCR-seq in 28 healthy mice. We uncovered hundreds of(More)
A large fraction of the world's most widespread and problematic pathogens, such as the influenza virus, seem to persist in nature by evading host immune responses by inducing immunity to genetically and phenotypically plastic epitopes (aka antigenic variation). The more recent re-emergence of pandemic influenza A/ H1N1 and avian H5N1 viruses has called(More)
The involvement of beta-amyloid (Abeta) in the pathogenesis of Alzheimer's disease (AD) has been well documented. In addition, a significant degree of information has been documented regarding the genetics of Abeta production and aggregation in familial forms of AD (FADs). However, the information regarding the causes or mechanism(s) responsible for Abeta(More)
The mechanisms by which adaptive phenotypes spread within an evolving population after their emergence are understood fairly well. Much less is known about the factors that influence the evolutionary accessibility of such phenotypes, a pre-requisite for their emergence in a population. Here, we investigate the influence of environmental quality on the(More)