In vitro model for the activation of CD4 and CD8 T cell receptors.
Previously, most models that sought to explain the misregulation of immune cell function assumed molecular similarities between the disease-causing pathogens and the host's proteins. In recent time several different models have been proposed and in this study, these concepts are compared to a new hypothesis proposing another explanation for this immune dysregulation: the possibility that the mislocalization of proteins may be responsible for autoimmune activity. Based on this hypothesis, proteins are recognized as self or non-self depending on where they appear in sufficiently high concentrations. To examine this new idea, the intracellular human proteins beta-actin, GAPDH, and hemoglobin as well as the extracellular human proteins insulin and albumin, were added to human whole blood samples. After an incubation period, the activation of whole-blood T lymphocytes in the samples was measured. The observed activation pattern of the T lymphocytes fit well with the proposed hypothesis. Therefore, these data suggest that protein mislocalization and/or errors within protein trafficking might be important in the development of autoimmune diseases.
Arneth
Borros M
BM
Institute of Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg University Mainz, Mainz, Germany. arneth@zentrallabor.klinik.uni-mainz.de
D000199:Actins / Q000276:immunology / Q000378:metabolism; D000418:Albumins / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002469:Cell Separation; D002478:Cells, Cultured; D003593:Cytoplasm / Q000276:immunology*; D005110:Extracellular Space / Q000276:immunology*; D005434:Flow Cytometry; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000276:immunology / Q000378:metabolism; D006454:Hemoglobins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D018448:Models, Immunological; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*
D000199:Actins; D000418:Albumins; D006454:Hemoglobins; D007328:Insulin; D011948:Receptors, Antigen, T-Cell; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases