<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Mechaninsms of Antigen Presentation : Role of non classical MHC Class II molecule H2-O/HLA-DO and Tetraspanin molecule CD82"^^ . "Summary Presentation of antigen by MHC class II molecules to CD4 T cells depends on the loading of antigenic peptides onto MHC class II molecules in endosomal compartments of antigen-presenting cells. There, efficient loading of peptides requires the assistance of the accessory molecule HLA-DM. DM is found tightly associated with another molecule, HLA-DO in humans, or H2-O in mice, but the function of DO is not entirely clear. MHC class II, DM, and DO are further associated with tetraspanins such as CD82, but their role in antigen presentation, if any, is also not clear. In this thesis, the function of DO and CD82 in antigen presentation was studied. 1. DO in antigen presentation. So far, the analysis of H2O-/- mice did not show a striking phenotype with regard to antigen presentation. Possible explanations are that the function of H2-O is allele-specific and does not affect presentation by Ab MHC class II molecules, the allele carried by H2-O-/- mice. Moreover, only few experimental systems are available for thorough testing of antigen presentation by th Ab allele. In this laboratory, transgenic mice were generated overexpressing H2-O, designated mDO mice, which express the Ak allele, and for which well-studied antigen presentation systems are available. The study presented here shows that DO downmodulates only presentation of epitopes that are loaded onto Ak molecules in early endocytic compartments, but not epitopes loaded in late endocytic compartments. Since DO is mainly expressed in B cells which predominantly take up antigen via their surface immunoglobulin (BCR, B cell receptor), we crossed the mDO with BCR transgenic mice. Again, DO downmodulated presentation of antigen only in the early endocytic compartment. These data suggest that DO may serve to skew antigen presentation to take place preferentially in late compartments. 2. CD82 in antigen presentation. We have concentrated on the tetraspanin CD82, because CD82 was shown to be associated with MHC class II, DM, and DO in MHC class II loading compartments. In addition, CD82 is known interact with other transmembrane molecules such as TCR, CD4, CD8, etc.. CD82-deficient mice were generated in this laboratory for the present study. Expression of a large panel of surface markers was found to be unchanged in CD82-deficient mice. However, T cells from CD82-/- mice were hyper reactive to stimulation by anti-CD3 and anti-CD28 antibodies, suggesting that CD82 affects the TCR signalling pathway. When CD82-deficient dendritic cells were analyzed, decreased antigen presentation was found, but again only loading of epitopes on the early endocytic compartments was affected, but not loading in late compartments. When splenocytes were used, were most antigen-presenting cells are B cells, no differences between CD82-/- and wild-type cells were found with regard to antigen presentation. These data demonstrate for the first time a role for a tetraspanin in antigen presentation and suggest that CD82 enhances antigen presentation not only in a compartment-specific manner, but also in a cell type-specific fashion. The respective mechanisms need to be explored in the future. It is, however, striking to note that both DO and CD82 affect antigen presentation only in the early endosomal compartment. This may suggest a functional link between DO and CD82."^^ . "2007" . . . . . . . . "Kishore J. R."^^ . "Kunapuli"^^ . "Kishore J. R. Kunapuli"^^ . . . . . . "Mechaninsms of Antigen Presentation : Role of non classical MHC Class II molecule H2-O/HLA-DO and Tetraspanin molecule CD82 (PDF)"^^ . . . "PhD_thesis_single_file.pdf"^^ . . . "Mechaninsms of Antigen Presentation : Role of non classical MHC Class II molecule H2-O/HLA-DO and Tetraspanin molecule CD82 (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Mechaninsms of Antigen Presentation : Role of non classical MHC Class II molecule H2-O/HLA-DO and Tetraspanin molecule CD82 (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Mechaninsms of Antigen Presentation : Role of non classical MHC Class II molecule H2-O/HLA-DO and Tetraspanin molecule CD82 (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Mechaninsms of Antigen Presentation : Role of non classical MHC Class II molecule H2-O/HLA-DO and Tetraspanin molecule CD82 (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Mechaninsms of Antigen Presentation : Role of non classical MHC Class II molecule H2-O/HLA-DO and Tetraspanin molecule CD82 (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #7661 \n\nMechaninsms of Antigen Presentation : Role of non classical MHC Class II molecule H2-O/HLA-DO and Tetraspanin molecule CD82\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .