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Some gene therapy strategies are compromised by the levels of gene expression required for therapeutic benefit, and also by the breadth of cell types that require correction.
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One factor to control the breadth of T cell responses is the surface morphology of a peptide MHC complex.
Eukaryotic cells are large enough to detect signals and then orient to them by differentiating the signal strength across the length and breadth of the cell.
Thus, if a single protein length peptide set is used, consensus or COT peptides are optimal for detecting responses, yet the breadth of T cell responses is extended with the use of coverage-optimized peptides.
Based on recent evidence that dendritic cells (DC) are important for activation of memory CD8+ T cell reactivity to influenza A virus, herpes simplex virus type 1 and human cytomegalovirus [14], [15], [16], [17], [18], we hypothesized that DC could enhance the breadth of T cell responses to HIV-1, particularly in persons on ART.
To analyze the impact of breadth of T cell immunity to Gag (i.e. other than KP9-specific responses), we performed intracellular cytokine staining assays for T cell activation using 5 pools of 25 overlapping 15mers peptides spanning the entire SIV Gag protein as previously described [27].
The study reported here provides a broad comparison of the magnitude, nature, and breadth of T cell responses induced by a DNA vaccine in the blood, lung, and gut of rhesus macaques and shows there can be significant differences in each compartment.
A glimpse of our lack of understanding of the breadth of T cell reactivity becomes apparent when analysing the MHC restriction of the epitopes identified to date.
DOI: http://dx.doi.org/10.7554/eLife.06585.001 Actin the most abundant protein in most eukaryotic cells assembles into a network of filaments that spans the length and breadth of the cell.
Several new vaccine vector approaches offer promise in the exquisite control of acute infection and in improving the breadth of T-cell responses.
The fixed cell images were obtained at ×63 magnification on a Zeiss Axioplan microscope with a 63×, 1.4 NA oil-immersion objective (Zeiss, Oberkochen, Germany), 2 taking 9 z stacks 300 nm apart, which completely encompassed the breadth of the cells, unless otherwise stated.
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