Major contribution of codominant CD8 and CD4 T cell epitopes to the human cytomegalovirus-specific T cell repertoire

Human cytomegalovirus (HCMV) infection or reactivation is a cause of morbidity and mortality in immunocompromised individuals. In immunocompetent individuals, in contrast, HCMV is successfully controlled by specific CD8 and CD4 T cells. Knowledge of CD8 and CD4 T cell epitopes from HCMV and their immunodominant features is crucial for the generation of epitope-specific T cells for adoptive immunotherapy and for the development of a peptide-based HCMV vaccine. Therefore, we investigated the natural frequencies of a large number of CD8 and CD4 T cell epitopes, including 10 novel ones. We determined several epitopes as immunodominant. Surprisingly, no clear hierarchies were found for CD8 T cell epitopes, indicating codominance. These results will be valuable for adoptive transfer strategies and support initiatives towards development of a peptide-based HCMV vaccine.Received 12 August 2004; received after revision 24 September 2004; accepted 29 October 2004 These authors contributed equally to this work.     

Zur Kinematik der Planetenbewegung in Copernicus' Commentariolus

Zusammenfassung Copernicus versucht, die Ptolemäischen Konstruktionen auf konzentrische Kreise und Epizykel zu reduzieren und aus ihnen ein wirklich einheitliches System zu schaffen. Bei der Umordnung, die er dazu vornimmt, bemüht er sich aber, so viel wie möglich vom Ptolemäischen System zu erhalten. Das punctum aequans ersetzt er bei den äußeren Planeten durch eine Näherungskonstruktion mit Hilfe eines Epizykels. Im Fall des Ptolemäischen Deferenten der Venus, der nach seinen Vorstellungen die Erdbahn wiedergibt, muß er einen dem punctum aequans annähernd gleichwertigen Epizykelmechanismus auf die Venusbahn verpflanzen. Vorgelegt von B. L. van der Waerden     

Dextranase-producing organisms in dental plaque from caries-free and caries-active naval recruits

Summary Dental plaque samples from caries-free and caries-active naval recruits were assayed for the prevalence of dextranase-producing organisms. These organisms were found in the plaque of all of the subjects. Mean percentages of dextranase-producing organisms with respect to total colony count for the 2 groups of subjects were not significantly different.The authors thank DTl Samuel Shelton and Mr Eric Mandel for technical assistance. The research was supported by Naval Medical Research and Development Command Project ZF58.524.012-0026, Bethesda, Maryland. The opinions expressed herein are those of the authors and are not to be construed as reflecting the views of the Navy Department or the Naval Service at large. The use of commercially available products does not imply endorsement of these products or preference to other similar products on the market.     

Rapid regulation of steroidogenesis by mitochondrial protein import

Most mitochondrial proteins are synthesized on cytoplasmic ribosomes and imported into mitochondria. The imported proteins are directed to one of four submitochondrial compartments--the outer mitochondrial membrane, the inner mitochondrial membrane, the intramembraneous space, or the matrix--where the protein then functions. Here we show that the steroidogenic acute regulatory protein (StAR), a mitochondrial protein required for stress responses, reproduction, and sexual differentiation of male fetuses, exerts its activity transiently at the outer mitochondrial membrane rather than at its final resting place in the matrix. We also show that its residence time at this outer membrane and its activity are regulated by its speed of mitochondrial import. This may be the first example of a mitochondrial protein exerting its biological activity in a compartment other than that to which it is finally targeted. This system enables steroidogenic cells to initiate and terminate massive levels of steroidogenesis within a few minutes, permitting the rapid regulation of serum steroid hormone concentrations.