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Publication : Non-canonicaly recruited TCRαβCD8αα IELs recognize microbial antigens.

First Author  Wojciech L Year  2018
Journal  Sci Rep Volume  8
Issue  1 Pages  10848
PubMed ID  30022086 Mgi Jnum  J:268715
Mgi Id  MGI:6271805 Doi  10.1038/s41598-018-29073-7
Citation  Wojciech L, et al. (2018) Non-canonicaly recruited TCRalphabetaCD8alphaalpha IELs recognize microbial antigens. Sci Rep 8(1):10848
abstractText  In the gut, various subsets of intraepithelial T cells (IELs) respond to self or non-self-antigens derived from the body, diet, commensal and pathogenic microbiota. Dominant subset of IELs in the small intestine are TCRalphabetaCD8alphaalpha(+) cells, which are derived from immature thymocytes that express self-reactive TCRs. Although most of TCRalphabetaCD8alphaalpha(+) IELs are thymus-derived, their repertoire adapts to microbial flora. Here, using high throughput TCR sequencing we examined how clonal diversity of TCRalphabetaCD8alphaalpha(+) IELs changes upon exposure to commensal-derived antigens. We found that fraction of CD8alphaalpha(+) IELs and CD4(+) T cells express identical alphabetaTCRs and this overlap raised parallel to a surge in the diversity of microbial flora. We also found that an opportunistic pathogen (Staphylococcus aureus) isolated from mouse small intestine specifically activated CD8alphaalpha(+) IELs and CD4(+) derived T cell hybridomas suggesting that some of TCRalphabetaCD8alphaalpha(+) clones with microbial specificities have extrathymic origin. We also report that CD8alphaalphaCD4(+) IELs and Foxp3CD4(+) T cells from the small intestine shared many alphabetaTCRs, regardless whether the later subset was isolated from Foxp3(CNS1) sufficient or Foxp3(CNS1) deficient mice that lacks peripherally-derived Tregs. Overall, our results imply that repertoire of TCRalphabetaCD8alphaalpha(+) in small intestine expends in situ in response to changes in microbial flora.
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