Journal article
Adaptable TCR avidity thresholds for negative selection
The Journal of immunology (1950), Vol.181(10), pp.6770-6778
11/15/2008
DOI: 10.4049/jimmunol.181.10.6770
PMID: 18981094
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.
Details
- Title: Subtitle
- Adaptable TCR avidity thresholds for negative selection
- Creators
- Milica Stojakovic - Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USALaura I Salazar-FontanaZohreh Tatari-CalderoneVladimir P BadovinacFabio R SantoriDamian KovalovskyDerek Sant'AngeloJohn T HartyStanislav Vukmanovic
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.181(10), pp.6770-6778
- Publisher
- United States
- DOI
- 10.4049/jimmunol.181.10.6770
- PMID
- 18981094
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- AI48837 / NIAID NIH HHS AI42767 / NIAID NIH HHS AI41573 / NIAID NIH HHS
- Language
- English
- Date published
- 11/15/2008
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984047671602771
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