Excess beta 2 microglobulin promoting functional peptide association with purified soluble class I MHC molecules

T lymphocytes expressing alpha beta receptors recognize antigenic peptide fragments bound to major histocompatibility complex class I or class II molecules present on the surface membranes of other cells. Peptide fragments are present in the two available HLA crystal structures and recent data indicate that peptide is required for the stable folding of the class I heavy chain and maintenance of its association with the class I light chain, beta 2-microglobulin (beta 2m), at physiological temperature. To explain how the exogenous peptide used to create targets for cytotoxic cells bearing CD8 antigen could associate with apparently peptide-filled extracellular class I molecules, we hypothesized that stable binding of exogenous peptide to mature class I molecules reflects either the replacement of previously bound peptide during the well documented beta 2m exchange process or the loading of 'empty' class I heavy chains dependent on the availability of excess beta 2m. In either case, free beta 2m should enhance peptide/class I binding. Using either isolated soluble class I molecules or living cells, we show here that free purified beta 2m markedly augments the generation of antigenic complexes capable of T-cell stimulation.     

Observations on an association between the weevil Scaphomorphus trivittatus (Say) and two Astragalus species on selenium-rich soils in Carbon County, Utah

The weevil Scaphomorphus trivittatus (Say) was found in close association with Astragalus praelongus var. elliseae (Rydb.) and Astragalus asclepiadoides (Jones) in selenium-containing soils in Carbon County, Utah. The weevils fed on roots of the Astragalus species and formed soil cocoons, which were attached to the tap roots. The weevils pupated and developed into adults in these cocoons over the fall and winter and then emerged in the spring. The plants and soil cocoons contained highly elevated levels of selenium compared to the soils. The weevils, in contrast, differed little from the soils in selenium content.     

Effect of iron supply on Southern Ocean CO2 uptake and implications for glacial atmospheric CO2

Photosynthesis by marine phytoplankton in the Southern Ocean, and the associated uptake of carbon, is thought to be currently limited by the availability of iron. One implication of this limitation is that a larger iron supply to the region in glacial times could have stimulated algal photosynthesis, leading to lower concentrations of atmospheric CO2. Similarly, it has been proposed that artificial iron fertilization of the oceans might increase future carbon sequestration. Here we report data from a whole-ecosystem test of the iron-limitation hypothesis in the Southern Ocean, which show that surface uptake of atmospheric CO2 and uptake ratios of silica to carbon by phytoplankton were strongly influenced by nanomolar increases of iron concentration. We use these results to inform a model of global carbon and ocean nutrients, forced with atmospheric iron fluxes to the region derived from the Vostok ice-core dust record. During glacial periods, predicted magnitudes and timings of atmospheric CO2 changes match ice-core records well. At glacial terminations, the model suggests that forcing of Southern Ocean biota by iron caused the initial approximately 40 p.p.m. of glacial-interglacial CO2 change, but other mechanisms must have accounted for the remaining 40 p.p.m. increase. The experiment also confirms that modest sequestration of atmospheric CO2 by artificial additions of iron to the Southern Ocean is in principle possible, although the period and geographical extent over which sequestration would be effective remain poorly known.     

The Clq receptor site on immunoglobulin G

We propose that, the binding site for the complement subcomponent Clq on immunoglobulin G involves the last two (C-terminal) beta-strands of the C gamma 2 domain. This region contains a large number of accessible and highly conserved charged residues and charge is postulated as an important component of the Clq-IgG interaction. The conclusions are reached on the basis of accessibility and sequence conservation analyses of C gamma 2 amino acid residues, the use of specific inhibitors and chemical modification studies.     

Renal conservation of antifreeze peptide in Antarctic eelpout, Rhigophila dearborni.

In Antarctic notothenioid fishes large amounts (3% w/v) of small molecular weights of 2,600-23,500 and would be expected to be filtered into the urine, they remain in the blood because the kidneys of these fishes contain only aglomerular nephrons. Unlike the situation in most fishes, urine formation is the result of secretion rather than filtration and reabsorption. On the other hand, the peptide antifreezes in Northern Hemisphere fishes such as the winter flounder. Pseudopleuronectes americanus, are retained by the glomerular kidney even though inulin, of comparable weight, is rapidly filtered from the blood into the urine. The Antarctic eelpout (zoarcid), Rhigophila dearborni, which is unrelated to either the Antarctic notothenioids or P. americanus, also uses a peptide antifreeze (molecular weight 6,000) which is maintained at a concentration of 3% (w/v) in the blood plasma. We report here that the lack of antifreeze in the urine of R. dearborni probably reflects the fact that the glomeruli are not functional and cannot filter. We support this conclusion with morphological and physiological evidence and relate our findings to the conservation of biological antifreeze necessary for life in ice-laden polar waters.     

Plasma protease inhibitors in mouse and man: divergence within the reactive centre regions

The plasma protease inhibitors control a wide variety of physiological functions including blood coagulation, complement activation and aspects of the inflammatory response. The inhibitors function by forming a 1:1 complex with a specific protease within the reactive centre region of the inhibitor. Little is known about the evolutionary relationships of these inhibitors. We report here the sequences of cDNAs which represent the C-terminal halves of the two major murine plasma protease inhibitors. One of these, murine alpha 1-antitrypsin, more appropriately called alpha 1-proteinase inhibitor (alpha 1-PI), has diverged from its human counterpart at a vital position in the reactive centre but this has not led to a physiologically significant change in function. Also, we have determined the partial sequence of a recently characterized protein termed contrapsin, which inhibits trypsin-like proteases. We show, surprisingly, that contrapsin is highly homologous to human alpha 1-antichymotrypsin, an inhibitor of chymotrypsin-like proteases. The reactive centre regions of these two inhibitors have diverged considerably, which may account for the differences in specificity. We propose that the genes for contrapsin and human alpha 1-antichymotrypsin are the descendents of a single gene that have evolved since rodent and primate divergence to encode proteins with different functions.