Non-canonicaly recruited TCRαβCD8αα IELs recognize microbial antigens

Scientific Reports
Lukasz WojciechLeszek Ignatowicz

Abstract

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 TCRαβCD8αα+ cells, which are derived from immature thymocytes that express self-reactive TCRs. Although most of TCRαβCD8αα+ IELs are thymus-derived, their repertoire adapts to microbial flora. Here, using high throughput TCR sequencing we examined how clonal diversity of TCRαβCD8αα+ IELs changes upon exposure to commensal-derived antigens. We found that fraction of CD8αα+ IELs and CD4+ T cells express identical αβTCRs 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 CD8αα+ IELs and CD4+ derived T cell hybridomas suggesting that some of TCRαβCD8αα+ clones with microbial specificities have extrathymic origin. We also report that CD8ααCD4+ IELs and Foxp3CD4+ T cells from the small intestine shared many αβTCRs, regardless whether the later subset was isolated from Foxp3CNS1 sufficient or Foxp3CNS1 deficient mice that lacks peripherally-derived Tregs. Overall, our...Continue Reading

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Citations

Feb 4, 2021·The Journal of Experimental Medicine·Sookjin MoonSeung-Woo Lee
Oct 23, 2020·International Journal of Molecular Sciences·Lukasz WojciechNicholas R J Gascoigne

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Methods Mentioned

BETA
transgenic
flow cytometry
PCR
electrophoresis

Software Mentioned

BioEdit
R
Ion Torrent Suite
Origin
BLAST

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