Adaptable TCR avidity thresholds for negative selection Journal Article
| Authors: | Stojakovic, M.; Salazar-Fontana, L. I.; Tatari-Calderone, Z.; Badovinac, V. P.; Santori, F. R.; Kovalovsky, D.; Sant'angelo, D.; Harty, J. T.; Vukmanovic, S. |
| Article Title: | Adaptable TCR avidity thresholds for negative selection |
| Abstract: | Central tolerance plays a significant role in preventing autoimmune diseases by eliminating T cells with high and intermediate avidity for self. To determine the manner of setting the threshold for deletion, we created a unique transgenic mouse strain with a diverse T cell population and globally increased TCR avidity for self-peptide/MHC complexes. Despite the adaptations aimed at reducing T cell reactivity (reduced TCR levels and increased levels of TCR signaling inhibitor CD5), transgenic mice displayed more severe experimental allergic encephalomyelitis and lupus. The numbers and activity of natural (CD4+CD25+) regulatory T cells were not altered. These findings demonstrate that the threshold for deletion is adaptable, allowing survival of T cells with higher avidity when TCR avidity is globally increased. Copyright © 2008 by The American Association of Immunologists, Inc. |
| Keywords: | signal transduction; controlled study; unclassified drug; nonhuman; flow cytometry; polymerase chain reaction; t lymphocyte; t-lymphocytes; mouse; animal; animals; mice; animal tissue; cell survival; animal experiment; animal model; pathology; immunoreactivity; mice, inbred c57bl; transgenic mouse; c57bl mouse; mice, transgenic; t lymphocyte receptor; cd4+ cd25+ t lymphocyte; immunological tolerance; biosynthesis; immunology; receptors, antigen, t-cell; autoantigen; autoantigens; autoimmunity; mouse strain; autoimmune diseases; autoimmune disease; major histocompatibility complex; cd5 antigen; lymphocyte antigen receptor; cell selection; allergic encephalomyelitis; antigens, cd5; self tolerance; lymphocyte subpopulation; cd5 protein, mouse; lupus vulgaris |
| Journal Title: | Journal of Immunology |
| Volume: | 181 |
| Issue: | 10 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2008-11-15 |
| Start Page: | 6770 |
| End Page: | 6778 |
| Language: | English |
| PUBMED: | 18981094 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 17 November 2011" - "CODEN: JOIMA" - "Source: Scopus" |
