Three dimensional structure directs T-cell epitope dominance associated with allergy.

BACKGROUND: CD4+ T-cell epitope immunodominance is not adequately explained by peptide selectivity in class II major histocompatibility proteins, but it has been correlated with adjacent segments of conformational flexibility in several antigens. METHODS: The published T-cell responses to two venom allergens and two aeroallergens were used to construct profiles of epitope dominance, which were correlated with the distribution of conformational flexibility, as measured by crystallographic B factors, solvent-accessible surface, COREX residue stability, and sequence entropy. RESULTS: Epitopes associated with allergy tended to be excluded from and lie adjacent to flexible segments of the allergen. CONCLUSION: During the initiation of allergy, the N- and/or C-terminal ends of proteolytic processing intermediates were preferentially loaded into antigen presenting proteins for the priming of CD4+ T cells.

Field-based detection and monitoring of uranium in contaminated groundwater using two immunosensors.

Field-based monitoring of environmental contaminants has long been a need for environmental scientists. Described herein are two kinetic exclusion-based immunosensors, a field portable sensor (FPS) and an inline senor, that were deployed at the Integrated Field Research Challenge Site of the U.S. Department of Energy in Rifle, CO. Both sensors utilized a monoclonal antibody that binds to a U(VI)-dicarboxyphenanthroline complex (DCPI in a kinetic exclusion immunoassay format These sensors were able to monitor changes of uranium in groundwater samples from approximately 1 microM to below the regulated drinking water limit of 126 nM (30 ppb). The FPS is a battery-operated sensor platform that can determine the uranium level in a single sample in 5-10 min, if the instrument has been previously calibrated with standards. The average minimum detection level (MDL) in this assay was 0.33 nM (79 ppt), and the MDL in the sample (based on a 1:200-1:400 dilution) was 66-132 nM (15.7-31.4 ppb). The inline sensor, while requiring a grounded power source, has the ability to autonomously analyze multiple samples in a single experiment The average MDL in this assay was 0.12 nM (29 ppt), and the MDL in the samples (based on 1:200 or 1:400 dilutions) was 24-48 nM (5.7-11.4 ppb). Both sensor platforms showed an acceptable level of agreement (9 = 0.94 and 0.76, for the inline and FPS, respectively) with conventional methods for uranium quantification.