Glycosylation signals that separate the trimerization from the mhc class II-binding domain control intracellular degradation of invariant chain.

Invariant chain (Ii) serves as a chaperone for folding and intracellular transport of major histocompatibility complex class II (MHCII) molecules. Early in biosynthesis, Ii associates with MHCII molecules and directs their intracellular transport to endocytic compartments where vesicular proteinases sequentially release Ii from the MHCII heterodimer. The detachment of Ii makes the MHCII groove susceptible for binding of antigenic peptides. We investigated the role of N-linked glycosylation in the controlled intracellular degradation of Ii. Motifs for asparagine-linked glycosylation were altered, and mutated Ii (IiNmut) was transiently expressed in COS cells. The half-life of IiNmut was strongly reduced compared with wild-type Ii although the sensitivity of the N glycan-free polypeptide to in vitro proteinase digestion was not substantially increased. Inhibition of vesicular proteinases revealed endosomal degradation of IiNmut. Intracellular proteolysis of IiNmut is substantially impaired by serine proteinase inhibitors. Thus, a considerable amount of IiNmut is degraded in nonacidic intracellular compartments. The data suggest that N-linked glycosylation of Ii hinders premature proteolysis in nonacidic vesicles resulting in Ii degradation in acidic MHC class II-processing compartments.

The influence of fasting on blood and plasma composition of herring gulls (Larus argentatus).

Populations of scavenging seabird species in the North Sea may fluctuate with an artificial food source: the availability of fishery waste. To document this impact, it is necessary to assess the birds' nutritional status during periods with decreased fishing activity. Reference data for this purpose was collected from 22 herring gulls investigated during laboratory fasting. After 6 d of food deprivation and body mass losses exceeding 15%, the first birds entered starvation phase 3. Comparatively, this is a rather weak fasting capacity. Plasma levels of total protein and thyroid hormones decreased and beta-hydroxybutyrate increased with fasting duration. The leucocyte proportions were shifted from lymphocytes to heterophils. After 3 d of refeeding, most of the fasting changes were reversed. Plasma enzyme activities increased and hematocrit, hemoglobin, and erythrocyte numbers decreased in both fasting and control birds, most likely as a result of experimental stress and repeated blood sampling. Glucose, cholesterol, monocytes, basophils, and glycosylated hemoglobin remained fairly constant. Triglycerides, free fatty acids, uric acid, and urea varied significantly, but changes were not as clearly a result of fasting. Therefore, total protein, beta-hydroxybutyrate, triiodothyronine, thyroxine, and lymphocyte and heterophil percentages may be the most reliable indicators of the nutritional status and the condition of free-living herring gulls.