Celiac disease is a genetic condition that results in a debilitating immune reaction in the gut to antigens in grain. The antigenic peptides recognized by the T cells that cause this disease are incompletely defined. Our understanding of the epitopes of pathogenic CD4(+ )T cells is based primarily on responses shown by intestinal T-cells in vitro to hydrolysates or polypeptides of gluten, the causative antigen. A protease-resistant 33-amino acid peptide from wheat alpha-gliadin is the immunodominant antigen, but little is known about the spectrum of T cell epitopes in rye and barley or the hierarchy of immunodominance and consistency of recognition of T-cell epitopes in vivo. We induced polyclonal gluten-specific T cells in the peripheral blood of celiac patients by feeding them cereal and performed a comprehensive, unbiased analysis of responses to all celiac toxic prolamins, a class of plant storage protein. The peptides that stimulated T cells were the same among patients who ate the same cereal, but were different after wheat, barley and rye ingestion. Unexpectedly, a sequence from omega-gliadin (wheat) and C-hordein (barley) but not alpha-gliadin was immunodominant regardless of the grain consumed. Furthermore, T cells specific for just three peptides accounted for the majority of gluten-specific T cells, and their recognition of gluten peptides was highly redundant. Our findings show that pathogenic T cells in celiac disease show limited diversity, and therefore suggest that peptide-based therapeutics for this disease and potentially other strongly HLA-restricted immune diseases should be possible.

The eubacterial population was studied in faecal samples of related and unrelated children. Temporal temperature gradient gel electrophoresis (TTGE) provided a snapshot of the bacterial population and allowed calculation of the degree of similarity in the predominant faecal microflora of identical twin pairs, fraternal twin pairs and unrelated paired controls. The highest levels of similarity were found in genetically identical twins. Significant differences were observed between the identical and fraternal twins (P ¼ 0 . 037), strongly suggesting a genetic influence over the composition of the faecal microflora. The unrelated control group had the lowest similarity and was significantly different from the twins (P ¼ 0 . 001). The results of this study indicate that host genetics influence the composition of the dominant eubacterial population in children.

The global pathogen Mycobacterium tuberculosis and other species in the suborder Corynebacterineae possess a distinctive outer membrane called the mycomembrane (MM). The MM is composed of mycolic acids, which are either covalently linked to an underlying arabinogalactan layer or incorporated into trehalose glycolipids that associate with the MM non-covalently. These structures are generated through a process called mycolylation, which is central to mycobacterial physiology and pathogenesis and is an important target for tuberculosis drug development. Current approaches to investigating mycolylation rely on arduous analytical methods that occur outside the context of a whole cell. Herein, we describe mycobacteria-specific chemical reporters that can selectively probe either covalent arabinogalactan mycolates or non-covalent trehalose mycolates in live mycobacteria. These probes, in conjunction with bioorthogonal chemistry, enable selective in situ detection of the major MM components.

Objective: To determine the effectiveness of an intensive quit‐smoking intervention on smoking rates at 36 weeks’ gestation among pregnant Aboriginal and Torres Strait Islander women. Design: Randomised controlled trial. Setting and participants: Pregnant Aboriginal and Torres Strait Islander women (n = 263) attending their first antenatal visit at one of three Aboriginal community‐controlled health services between June 2005 and December 2009. Intervention: A general practitioner and other health care workers delivered tailored advice and support to quit smoking to women at their first antenatal visit, using evidence‐based communication skills and engaging the woman's partner and other adults in supporting the quit attempts. Nicotine replacement therapy was offered after two failed attempts to quit. The control (“usual care”) group received advice to quit smoking and further support and advice by the GP at scheduled antenatal visits. Main outcome measure: Self‐reported smoking status (validated with a urine cotinine measurement) between 36 weeks’ gestation and delivery. Results: Participants in the intervention group (n = 148) and usual care group (n = 115) were similar in baseline characteristics, except that there were more women who had recently quit smoking in the intervention group than the control group. At 36 weeks, there was no significant difference between smoking rates in the intervention group (89%) and the usual care group (95%) (risk ratio for smoking in the intervention group relative to usual care group, 0.93 [95% CI, 0.86–1.08]; P = 0.212). Smoking rates in the two groups remained similar when baseline recent quitters were excluded from the analysis. Conclusion: An intensive quit‐smoking intervention was no more effective than usual care in assisting pregnant Aboriginal and Torres Strait Islander women to quit smoking during pregnancy. Contamination of the intervention across groups, or the nature of the intervention itself, may have contributed to this result. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12609000929202.