Identification of CD4+ T Cell Epitopes in C. burnetii Antigens Targeted by Antibody Responses

Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes acute Q fever and chronic infections in humans. A killed, whole cell vaccine is efficacious, but vaccination can result in severe local or systemic adverse reactions. Although T cell responses are considered pivotal for vaccine derived protective immunity, the epitope targets of CD4+ T cell responses in C. burnetii vaccination have not been elucidated. Since mapping CD4+ epitopes in a genome with over 2,000 ORFs is resource intensive, we focused on 7 antigens that were known to be targeted by antibody responses. 117 candidate peptides were selected from these antigens based on bioinformatics predictions of binding to the murine MHC class II molecule H-2 IAb. We screened these peptides for recognition by IFN-γ producing CD4+ T cell in phase I C. burnetii whole cell vaccine (PI-WCV) vaccinated C57BL/6 mice and identified 8 distinct epitopes from four different proteins. The identified epitope targets account for 8% of the total vaccination induced IFN-γ producing CD4+ T cells. Given that less than 0.4% of the antigens contained in C. burnetii were screened, this suggests that prioritizing antigens targeted by antibody responses is an efficient strategy to identify at least a subset of CD4+ targets in large pathogens. Finally, we examined the nature of linkage between CD4+ T cell and antibody responses in PI-WCV vaccinated mice. We found a surprisingly non-uniform pattern in the help provided by epitope specific CD4+ T cells for antibody production, which can be specific for the epitope source antigen as well as non-specific. This suggests that a complete map of CD4+ response targets in PI-WCV vaccinated mice will likely include antigens against which no antibody responses are made

Population mechanics: A mathematical framework to study T cell homeostasis

Unlike other cell types, T cells do not form spatially arranged tissues, but move independently throughout the body. Accordingly, the number of T cells in the organism does not depend on physical constraints imposed by the shape or size of specific organs. Instead, it is determined by competition for interleukins. From the perspective of classical population dynamics, competition for resources seems to be at odds with the observed high clone diversity, leading to the so-called diversity paradox. In this work we make use of population mechanics, a non-standard theoretical approach to T cell homeostasis that accounts for clone diversity as arising from competition for interleukins. The proposed models show that carrying capacities of T cell populations naturally emerge from the balance between interleukins production and consumption. These models also suggest remarkable functional differences in the maintenance of diversity in naïve and memory pools. In particular, the distribution of memory clones would be biased towards clones activated more recently, or responding to more aggressive pathogenic threats. In contrast, permanence of naïve T cell clones would be determined by their affinity for cognate antigens. From this viewpoint, positive and negative selection can be understood as mechanisms to maximize naïve T cell diversity

Sorry, Your Order Has a Substitution : The Effects of Substitution Policy in Online Grocery Retailing

Post-purchase out-of-stock (OOS) often happens in an online store context, where products appear to be available at the time a consumer makes an order and checks out, but then become OOS when the order is to be dispatched. To mitigate negative responses from consumers, online grocery retailers often provide consumers a substitution alternative to the OOS item. This paper investigates the effects of two substitution policies where we focus on different matching strategies of the substitution with the OOS item. In policy one, we measure the effect of matching on the dominant attribute (brand vs. flavour). In policy two, we test the effect of matching with a product from the consumers’ past purchase portfolio. We investigate these two substitution policies and their interaction in two categories that differ on the level of differentiation (i.e., the degree to which distinctions are objectively measurable – vertical differentiation/VD vs. not easy to evaluate – horizontal differentiation/HD). Our dependent variable is the probability to accept the substitute. The study employs a computer-simulated purchase experiment, using two product categories: margarine (VD) and cereals (HD). 2,113 UK consumers representative of general UK shopper profile participated. Findings show that in the margarine category where brand is the dominant attribute, the same brand substitution is more likely to be accepted than the same flavour substitution. In contrast, in the cereal category where flavour is more likely to be the dominant attribute, same flavour substitution is more likely to be accepted than same brand substitution. The results also show that, in both categories, matching the substitution product with a product from consumers’ past purchase portfolio is more likely to be accepted than offering a substitute that consumers have not bought before. We also found a significant interaction between the two policy types but for cereals only. The effects of two substitution policies are mediated by perceived fairness of the substitution. The paper discusses contributions and implication for future research

Self-concept of Indigenous and non-Indigenous Australian students: Competence and affect components and relations to achievement

Previous research on differences and similarities in self-concept of Indigenous and non-Indigenous Australian students did not consider the possible differentiation between competence and affect components. As a result, it is unknown whether previously found differences between Indigenous and non-Indigenous students' self-concepts are the result of their beliefs about their abilities or their feelings about specific domains. Thus, the present study aims to examine and compare the structure, the mean levels, and the relations to achievement measures of Indigenous and non-Indigenous Australian students' self-concepts in academic and non-academic domains when taking the competence-affect separation into account. Self-concepts in math, English, school, physical ability, and art were measured with 1809 secondary school students including 343 Indigenous students. For Indigenous and non-Indigenous students, confirmatory factor analyses demonstrated that all self-concept facets measured could be separated into competence and affect components although the correlations between competence and affect components were high, particularly for art and physical ability self-concepts. Non-Indigenous students demonstrated higher levels of school competence, English competence, English affect, and math competence self-concepts. Indigenous students displayed higher levels of physical ability competence self-concept while no group differences could be found for school affect, math affect, physical ability affect, and art competence and art affect self-concepts. Invariance tests revealed an invariant factor structure and invariant relations between the multiple self-concept facets and achievement factors across Indigenous and non-Indigenous students. Hence, the present study adds to our understanding of the similarities and differences regarding Indigenous and non-Indigenous Australian students' self-concepts. © 2014 Elsevier Inc

Competence and affect dimensions of self-concept among higher education students: a factorial validation study of an academic subject-specific self-concept

A hierarchical and multi-dimensional model of self-concept is well-validated. Despite increasing evidence that self-concept comprises two latent factors related to perceptions of ‘competence’ and ‘affect’, many researchers continue to examine the impact of a unitary self-concept on educational outcomes. This study explores evidence for a 2-factor academic subject-specific self-concept factor structure and examines the association between these factors with self-efficacy in a sample of higher education students. Participants from two studies (N = 314; N = 475) were enrolled in introductory psychology courses. Exploratory (EFA) and confirmatory (CFA) factor analysis examined and confirmed the factor structure of two oblique self-concept factors, reflecting affect and competence, in both studies. Temporal invariance of the 2-factor model was supported. Despite a substantial literature that discriminates between self-concept and self-efficacy, self-efficacy appears to be itself a facet of competency self-concept

Profile formation of academic self-concept in elementary school students in grades 1 to 4.

Academic self-concept (ASC) is comprised of individual perceptions of one's own academic ability. In a cross-sectional quasi-representative sample of 3,779 German elementary school children in grades 1 to 4, we investigated (a) the structure of ASC, (b) ASC profile formation, an aspect of differentiation that is reflected in lower correlations between domain-specific ASCs with increasing grade level, (c) the impact of (internal) dimensional comparisons of one's own ability in different school subjects for profile formation of ASC, and (d) the role played by differences in school grades between subjects for these dimensional comparisons. The nested Marsh/Shavelson model, with general ASC at the apex and math, writing, and reading ASC as specific factors nested under general ASC fitted the data at all grade levels. A first-order factor model with math, writing, reading, and general ASCs as correlated factors provided a good fit, too. ASC profile formation became apparent during the first two to three years of school. Dimensional comparisons across subjects contributed to ASC profile formation. School grades enhanced these comparisons, especially when achievement profiles were uneven. In part, findings depended on the assumed structural model of ASCs. Implications for further research are discussed with special regard to factors influencing and moderating dimensional comparisons