Local wood demand, land cover change and the state of Albany Thicket on an urban commonage in the Eastern Cape, South Africa.

Understanding the rates and causes of land-use change is crucial in identifying solutions, especially in sensitive landscapes and ecosystems, as well as in places undergoing rapid political, socioeconomic or ecological change. Despite considerable concern at the rate of transformation and degradation of the biodiversity-rich Albany Thicket biome in South Africa, most knowledge is gleaned from private commercial lands and state conservation areas. In comparison, there is limited work in communal areas where land uses include biomass extraction, especially for firewood and construction timber. We used aerial photographs to analyze land use and cover change in the high- and low-use zones of an urban commonage and an adjacent protected area over almost six decades, which included a major political transition. Field sampling was undertaken to characterize the current state of the vegetation and soils of the commonage and protected area and to determine the supply and demand for firewood and construction timber. Between the 1950s and 1980s, there was a clear increase in woody vegetation cover, which was reversed after the political transition in the mid-1990s. However, current woody plant standing stocks and sustainable annual production rates are well above current firewood demand, suggesting other probable causes for the decline in woody plant cover. The fragmentation of woody plant cover is paralleled by increases in grassy areas and bare ground, an increase in soil compaction, and decreases in soil moisture, carbon, and nutrients.

The human G1m1 allotype associates with CD4+ T-cell responsiveness to a highly conserved IgG1 constant region peptide and confers an asparaginyl endopeptidase cleavage site.

The human G1m1 allotype comprises two amino acids, D12 and L14, in the CH3 domain of IGHG1. Although the G1m1 allotype is prevalent in human populations, ~40% of Caucasiods are homozygous for the nG1m1 allotype corresponding to E12 and M14. Peptides derived from the G1m1 region were tested for their ability to induce CD4+ T-cell proliferative responses in vitro. A peptide immediately downstream from the G1m1 sequence was recognized by CD4+ T cells in a large percentage of donors (peptide CH315-29). CD4+ T-cell proliferative responses to CH315-29 were found at an increased frequency in nG1m1 homozygous donors. Homozygous nG1m1 donors possessing the HLA-DRB1*07 allele displayed the highest magnitudes of proliferation. CD4+ T cells from donors homozygous for nG1m1 proliferated to G1m1-carrying Fc-fragment proteins, whereas CD4+ T cells from G1m1 homozygous donors did not. The G1m1 sequence creates an enzymatic cleavage site for asparaginyl endopeptidase in vitro. Proteolytic activity at D12 may allow the presentation of the CH315-29 peptide, which in turn may result in the establishment of tolerance to this peptide in G1m1-positive donors. Homozygous nG1m1 patients may be more likely to develop CD4+ T-cell-mediated immune responses to therapeutic antibodies carrying the G1m1 allotype.

CD4+ T-cell epitope determination using unexposed human donor peripheral blood mononuclear cells.

The engineering of protein therapeutics to improve their stability, their efficacy, or to create "humanized" versions introduces changes to the amino acid sequence that are potential T-cell epitopes. Until now, there has been no available assay to detect primary T-cell responses to novel epitopes in humans. Currently available in vitro protocols for epitope determination rely on peripheral blood lymphocytes from environmentally exposed or disease-bearing donors. This severely limits the opportunity to confirm T-cell epitopes in novel proteins, because exposed donors are not available to novel or engineered proteins. Other methods for determining T-cell epitopes are either computer-modeled predictions based on potential binding to HLA molecules or the identification of peptides presented by HLA molecules removed from the surface of tumor cells or protein-pulsed antigen-presenting cells. Because HLA binding is necessary, but not sufficient, for T-cell responses, these methods must be validated by in vitro presentation assays. The authors describe a dendritic cell-based assay that identifies CD4+ T-cell epitopes in novel proteins using unexposed donors. Predicted T-cell epitopes in the protein of interest were confirmed using cells from two verified exposed donors. The major CD4+ T-cell epitope of the novel protein examined in this study associated with the expression of HLA DRb1*15. This assay reflects de novo priming in vitro, and it accurately identifies primary T-cell epitopes. This assay is a powerful tool for determining relevant immunostimulatory T-cell epitopes for all types of immunoregulatory applications.