Recognition principle of the TAP transporter disclosed by combinatorial peptide libraries

Transport of peptides across the membrane of the endoplasmic reticulum for assembly with MHC class I molecules is an essential step in antigen presentation to cytotoxic T cells. This task is performed by the major histocompatibility complex-encoded transporter associated with antigen processing (TAP). Using a combinatorial approach we have analyzed the substrate specificity of human TAP at high resolution and in the absence of any given sequence context, revealing the contribution of each peptide residue in stabilizing binding to TAP. Human TAP was found to be highly selective with peptide affinities covering at least three orders of magnitude. Interestingly, the selectivity is not equally distributed over the substrate. Only the N-terminal three positions and the C-terminal residue are critical, whereas effects from other peptide positions are negligible. A major influence from the peptide backbone was uncovered by peptide scans and libraries containing d amino acids. Again, independent of peptide length, critical positions were clustered near the peptide termini. These approaches demonstrate that human TAP is selective, with residues determining the affinity located in distinct regions, and point to the role of the peptide backbone in binding to TAP. This binding mode of TAP has implications in an optimized repertoire selection and in a coevolution with the major histocompatibility complex/T cell receptor complex.

Cape of Good Hope and Cape Town Region, South Africa, Nautical Chart, 1822 (Raster Image)

This layer is a georeferenced raster image of the historic, paper map entitled: Survey of the Cape of Good Hope, by Lieut. A.T.E. Vidal of H.M.S. Leven, assisted by Captn. Chas. Lechmere, R.N. Lieut T. Boteler, and Mr. H.A. Gibbons, Admlty. Midn. under the direction of Captn. W.F.W. Owen, 1822. J. & C. Walker sculpt. It was published according to Act of Parliament at the Hydrographical Office of the Admiralty, 4th March 1828. Scale [ca. 1:153,512]. Covers the Cape Peninsula region, including False Bay and Cape Town, South Africa. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'WGS 1984 UTM 34S' coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows coastal features such as beacons, rocks, channels, points, coves, islands, bottom soil types, anchorage points, and more. Includes also selected land features such as roads, drainage, land cover, selected buildings, towns, and more. Relief shown by contours; depths by soundings. Includes notes, table of heights, and two views. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.