T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis

Chronic relapsing paralysis and demyelination within the central nervous system (CNS), features associated with the human disease multiple sclerosis (MS), develop in mice after injection of murine T-cell clones specific for the autoantigen myelin basic protein (MBP). We examined the fine specificity of three independently derived encephalitogenic T-cell clones using synthetic polypeptides derived from portions of the N-terminal sequence of MBP. These clones appear functionally identical; they all respond to an epitope in the N-terminal nine amino acid residues in association with the same class II (I-A) molecules of the major histocompatibility complex (MHC). Both the N-terminal acetyl moiety and the first residue (Ala) are necessary for recognition. Only N-terminal MBP peptides recognized by these clones were found to cause encephalomyelitis (EAE) in vivo. These results show that the N-terminal MBP-specific T lymphocytes that mediate autoimmune encephalomyelitis are a small population with a limited repertoire; they all recognise the same combination of MHC and target.     

Stereoselectivity in peptide synthesis under simple conditions

Zusammenfassung Die Umsetzung vond,l-Leucin mit verschiedenenl-Aminosäuren und Dicyanamid als Kondensationsmittel zu Oligopeptiden verläuft nicht stereoselektiv. Die Bedeutung dieser Beobachtung in bezug auf den Ursprung des Lebens wird diskutiert.     

Cell-like structures from simple molecules under simulated primitive earth conditions

Résumé Le sulfocyanate d'ammonium et l'aldéhyde formique, formés probablement au cours de l'évolution géochimique, fournissent les structures ressemblant à des cellules. La formation des ces structures, sous des conditions variables de concentration, est catalysée par les irradations UV. Ces formes protocellulaires expulsent leurs contenus vacuolaires et absorbent des matières colorantes. La transition de l'évolution géochimique aux protocellules semble être une étape admissible selon le résultat de nos expériences.

---

---

Supported by the National Research Council (Canada) Grant No. A-2528 and the National Aeronautics and Space Administration (PSU institutional grant). We thankR. Huyer for photographic assistance.     

The potential therapeutic role of statins in central nervous system autoimmune disorders

3-Hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins are widely used oral cholesterol-lowering drugs. Statins competitively inhibit HMG-CoA reductase, the enzyme that catalyzes conversion of HMG-CoA to L-mevalonate, a key intermediate in cholesterol synthesis. Certain metabolites of mevalonate are also involved in posttranslational modification of specific proteins involved in cell proliferation and differentiation. Thus, statins have important biologic effects that may be independent of their cholesterol-reducing properties. Recent studies indicate that statins have antiinflammatory and neuroprotective properties which may be beneficial in the treatment of multiple sclerosis as well as other central nervous system (CNS) neurodegenerative diseases. This article will outline current experimental evidence that may suggest potential clinical benefits for patients with CNS autoimmune disorders. Ultimately, clinical trials will have to determine the safety and efficacy of statins in this patient population.Received 17 April 2003; received after revision 21 May 2003; accepted 22 May 2003     

Possible abiotic origin of precambrian microfossils

Résumé Les microsphères obtenues par irradiation UV du thiocyanate d'ammonium sont comparées du point de vue morphologique, chimique et de certaines propriétés physiques, à certains microfossiles précambriens.     

Taking dendritic cells into medicine

Dendritic cells (DCs) orchestrate a repertoire of immune responses that bring about resistance to infection and silencing or tolerance to self. In the settings of infection and cancer, microbes and tumours can exploit DCs to evade immunity, but DCs also can generate resistance, a capacity that is readily enhanced with DC-targeted vaccines. During allergy, autoimmunity and transplant rejection, DCs instigate unwanted responses that cause disease, but, again, DCs can be harnessed to silence these conditions with novel therapies. Here we present some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy.