Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study

Abstract Background The placenta is an important site for iron metabolism in humans. It transfers iron from the mother to the fetus. One of the major iron transport proteins is transferrin, which is a blood plasma protein crucial for iron uptake. Its localization and expression may be one of the markers to distinguish placental dysfunction. Methods In the experimental study we used antibody preparation, mass spectrometric analysis, biochemical and immunocytochemical methods for characterization of transferrin expression on the human choriocarcinoma cell line JAR (JAR cells), placental lysates, and cryostat sections. Newly designed monoclonal antibody TRO-tf-01 to human transferrin was applied on human placentae from normal (n = 3) and abnormal (n = 9) pregnancies. Results Variations of transferrin expression were detected in villous syncytiotrophoblast, which is in direct contact with maternal blood. In placentae from normal pregnancies, the expression of transferrin in the syncytium was significantly lower (p Conclusion These observations suggest that in the case of abnormal pregnancies, the fetus may require higher levels of transferrin in order to prevent iron depletion due to the stress from the placental dysfunction.</p

The kinetic basis of peptide exchange catalysis by HLA-DM

The mechanism by which the peptide exchange factor HLA-DM catalyzes peptide loading onto structurally homologous class II MHC proteins is an outstanding problem in antigen presentation. The peptide-loading reaction of class II MHC proteins is complex and includes conformational changes in both empty and peptide-bound forms in addition to a bimolecular binding step. By using a fluorescence energy transfer assay to follow the kinetics of peptide binding to the human class II MHC protein HLA-DR1, we find that HLA-DM catalyzes peptide exchange by facilitating a conformational change in the peptide-bound complex, and not by promoting the bimolecular MHC–peptide reaction or the conversion between peptide-receptive and -averse forms of the empty protein. Thus, HLA-DM serves essentially as a protein-folding or conformational catalyst

Sex-specific differences in peripheral microvascular blood flow in preterm infants

Microvascular blood flow is related to physiologic instability in newborn preterm infants. We investigated sex-specific differences in basal microvascular blood flow and the ability of the microvasculature to respond to vasoactive stimuli following preterm birth. Ninety-six infants in two gestational age groups (24-28 and 29-36 wk) were studied on days 1-5 of life. Laser Doppler flowmetry was used to measure baseline microvascular blood flow and vasodilatation in response to acetylcholine and local warming. A significant interaction of gestational age and sex was observed for baseline flow at 24 h of age. In the 24-28 wk group, male infants had higher baseline flow than females. Male, but not female, infants born at 24-28 wk exhibited a significant relationship between baseline flow and vasodilatory response to acetylcholine at 24 h of age. By 120 h of age, both sexes exhibited similar responses. Infants born at 24-28 wk exhibited greater vasodilatation in response to local warming than those born at 29-36 wk at 24, 72, and 120 h of age. Sex-specific differences in microvascular blood flow and vasodilatory capacity in the immediate newborn period may affect the transitional circulation, contributing to excess of morbidity and mortality in preterm males

Footprints of antigen processing boost MHC class II natural ligand predictions

Abstract Background Major histocompatibility complex class II (MHC-II) molecules present peptide fragments to T cells for immune recognition. Current predictors for peptide to MHC-II binding are trained on binding affinity data, generated in vitro and therefore lacking information about antigen processing. Methods We generate prediction models of peptide to MHC-II binding trained with naturally eluted ligands derived from mass spectrometry in addition to peptide binding affinity data sets. Results We show that integrated prediction models incorporate identifiable rules of antigen processing. In fact, we observed detectable signals of protease cleavage at defined positions of the ligands. We also hypothesize a role of the length of the terminal ligand protrusions for trimming the peptide to the MHC presented ligand. Conclusions The results of integrating binding affinity and eluted ligand data in a combined model demonstrate improved performance for the prediction of MHC-II ligands and T cell epitopes and foreshadow a new generation of improved peptide to MHC-II prediction tools accounting for the plurality of factors that determine natural presentation of antigens