61 research outputs found
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Somatic Variation of T-Cell Receptor Genes Strongly Associate with HLA Class Restriction
Every person carries a vast repertoire of CD4+ T-helper cells and CD8+ cytotoxic T cells for a healthy immune system. Somatic VDJ recombination at genomic loci that encode the T-cell receptor (TCR) is a key step during T-cell development, but how a single T cell commits to become either CD4+ or CD8+ is poorly understood. To evaluate the influence of TCR sequence variation on CD4+/CD8+ lineage commitment, we sequenced rearranged TCRs for both α and β chains in naïve T cells isolated from healthy donors and investigated gene segment usage and recombination patterns in CD4+ and CD8+ T-cell subsets. Our data demonstrate that most V and J gene segments are strongly biased in the naïve CD4+ and CD8+ subsets with some segments increasing the odds of being CD4+ (or CD8+) up to five-fold. These V and J gene associations are highly reproducible across individuals and independent of classical HLA genotype, explaining ~11% of the observed variance in the CD4+ vs. CD8+ propensity. In addition, we identified a strong independent association of the electrostatic charge of the complementarity determining region 3 (CDR3) in both α and β chains, where a positively charged CDR3 is associated with CD4+ lineage and a negatively charged CDR3 with CD8+ lineage. Our findings suggest that somatic variation in different parts of the TCR influences T-cell lineage commitment in a predominantly additive fashion. This notion can help delineate how certain structural features of the TCR-peptide-HLA complex influence thymic selection
Caring for children: the childcare dilemmas that working parents face
More and more women with young or school-age children are now going out to work. If the father works as well, parents have to choose between formal paid childcare and informal unpaid childcare. Informal childcare is the most common resort of people with a low level of education, but because increasing numbers of older women and women with children are now going out to work, the supply of informal childcare is shrinking and, as a result, it is becoming increasingly difficult for people with a low level of education to combine work and childcare
Summary policy implications regarding children and child-friendly policies Deliverable no 21Report prepared under the project "DIALOG - Population Policy Acceptance Study - the viewpoint of citizens and policy actors regarding the management of population related change"
Welk gezinsbeleid leidt tot meer kinderen?: meningen over overheidsmaatregelen onderzocht
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