The capacity of dendritic cells to initiate T cell responses is related to their ability to redistribute MHC class II molecules from the intracellular MHC class II compartments to the cell surface. This redistribution occurs during dendritic cell development as they are converted from an antigen capturing, immature dendritic cell into an MHC class IIpeptide presenting mature dendritic cell. During this maturation, antigen uptake and processing are down-regulated and peptide-loaded class II complexes become expressed in a stable manner on the cell surface. Here we report that the tetraspanin CD63, that associates with intracellularly localized MHC class II molecules in immature dendritic cells, was modified post-translationally by poly N-acetyl lactosamine addition during maturation. This modification of CD63 was accompanied by a change in morphology of MHC class II compartments from typical multivesicular organelles to structures containing densely packed lipid moieties. Post-translational modification of CD63 may be involved in the functional and morphological changes of MHC class II compartments that occur during dendritic cell maturation.Keywords: antigen presentation; poly N-acetyl lactosamine addition; dendritic cells; tetraspanins; MHC class II.Dendritic cells have the unique feature to induce T cell responses in lymphoid organs against antigens captured in peripheral tissues (for review, see [1,2]). Immature tissue dendritic cells use several mechanisms to internalize a broad array of antigens via the endosomal-lysosomal pathway including fluid phase endocytosis, macropinocytosis and several receptor-dependent mechanisms [3][4][5]. Peptides derived from internalized antigens are loaded onto class II molecules in MHC class II compartments [6][7][8][9]. After migration to lymph nodes upon inflammation or an infection, mature dendritic cells present these MHC class II-peptide complexes to T lymphocytes.Several co-ordinated changes enable efficient presentation of epitopes generated at sites of inflammation to T lymphocytes for prolonged periods of time [10,11]. During maturation of dendritic cells, the number of MHC class II-peptide complexes that are generated is increased, both by a transient up-regulation of synthesis as well as by an increase in half-life of MHC class II molecules [10]. In addition, uptake and processing of antigen is downregulated and MHC class II molecules are redistributed to the cell surface. Trafficking of MHC class II-peptide complexes is in part regulated by the protease, cathepsin S, that is activated upon maturation of dendritic cells [12,13]. This protease removes the sorting signal in the cytoplasmic tail of the invariant chain, a protein involved in targeting newly synthesized MHC class II molecules to MHC class II compartments [14][15][16], thus allowing MHC class II molecules to exit these organelles. Moreover, maturation induces a reduction of internalization and degradation of cell surface MHC class II molecules [17]. These mechanisms result in the stable expression of MH...
We have developed an experimental system for linking information on cell-free transcription and translation products from cDNA clones with data obtained from hybridization signals from complex probes. The work described in this paper consists of two distinct processes, one being the construction of a system of clonal addresses and the other the identification of expressed genes involved in the studied processes. We describe the use of this system to identify genes involved in thymus development. Complex probes from fetal thymuses (GD15, 17 and newborn) of Balb/c mice were used to identify genes, which are up- or downregulated during the process of differentiation. The full set of information is available in the Clone-base of the Basel Institute for Immunology and will be retrievable from the website of the collaborating laboratories.
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