Prevention of Cytotoxic T Cell Escape Using a Heteroclitic Subdominant Viral T Cell Determinant

High affinity antigen-specific T cells play a critical role during protective immune responses. Epitope enhancement can elicit more potent T cell responses and can subsequently lead to a stronger memory pool; however, the molecular basis of such enhancement is unclear. We used the consensus peptide-binding motif for the Major Histocompatibility Complex molecule H-2Kb to design a heteroclitic version of the mouse hepatitis virus-specific subdominant S598 determinant. We demonstrate that a single amino acid substitution at a secondary anchor residue (Q to Y at position 3) increased the stability of the engineered determinant in complex with H-2Kb. The structural basis for this enhanced stability was associated with local alterations in the pMHC conformation as a result of the Q to Y substitution. Recombinant viruses encoding this engineered determinant primed CTL responses that also reacted to the wildtype epitope with significantly higher functional avidity, and protected against selection of virus mutated at a second CTL determinant and consequent disease progression in persistently infected mice. Collectively, our findings provide a basis for the enhanced immunogenicity of an engineered determinant that will serve as a template for guiding the development of heteroclitic T cell determinants with applications in prevention of CTL escape in chronic viral infections as well as in tumor immunity

Genomic microsatellites identify shared Jewish ancestry intermediate between Middle Eastern and European populations

<p>Abstract</p> <p>Background</p> <p>Genetic studies have often produced conflicting results on the question of whether distant Jewish populations in different geographic locations share greater genetic similarity to each other or instead, to nearby non-Jewish populations. We perform a genome-wide population-genetic study of Jewish populations, analyzing 678 autosomal microsatellite loci in 78 individuals from four Jewish groups together with similar data on 321 individuals from 12 non-Jewish Middle Eastern and European populations.</p> <p>Results</p> <p>We find that the Jewish populations show a high level of genetic similarity to each other, clustering together in several types of analysis of population structure. Further, Bayesian clustering, neighbor-joining trees, and multidimensional scaling place the Jewish populations as intermediate between the non-Jewish Middle Eastern and European populations.</p> <p>Conclusion</p> <p>These results support the view that the Jewish populations largely share a common Middle Eastern ancestry and that over their history they have undergone varying degrees of admixture with non-Jewish populations of European descent.</p

On-farm maize storage systems and rodent postharvest losses in six maize growing agro-ecological zones of Kenya

Rodents are one of the major postharvest pests that affect food security by impacting on both food availability and safety. However, knowledge of the impact of rodents in on-farm maize storage systems in Kenya is limited. A survey was conducted in 2014 to assess magnitudes of postharvest losses in on-farm maize storage systems in Kenya, and the contribution of rodents to the losses. A total of 630 farmers spread across six maize growing agro-ecological zones (AEZs) were interviewed. Insects, rodents and moulds were the main storage problems reported by farmers. Storage losses were highest in the moist transitional and moist mid-altitude zones, and lowest in the dry-transitional zone. Overall, rodents represented the second most important cause of storage losses after insects, and were ranked as the main storage problem in the lowland tropical zone, while insects were the main storage problem in the other AEZs. Where maize was stored on cobs, total farmer perceived (farmer estimation) storage weight losses were 11.1 ± 0.7 %, with rodents causing up to 43 % of these losses. Contrastingly, where maize was stored as shelled grain, the losses were 15.5 ± 0.6 % with rodents accounting for up to 30 %. Regression analysis showed that rodents contributed significantly to total storage losses (p < 0.0001), and identified rodent trapping as the main storage practice that significantly (p = 0.001) lowered the losses. Together with insecticides, rodent traps were found to significantly decrease total losses. Improved awareness and application of these practices could mitigate losses in on farm-stored maize