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Mucosal Immunol. 2019 Nov 14. doi: 10.1038/s41385-019-0222-9. [Epub ahead of print]

Single-cell TCR sequencing of gut intraepithelial γδ T cells reveals a vast and diverse repertoire in celiac disease.

Author information

1
K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo, 0424, Oslo, Norway. l.m.eggesbo@medisin.uio.no.
2
K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo, 0424, Oslo, Norway.
3
Department of Immunology, University of Oslo and Oslo University Hospital- Rikshospitalet, 0372, Oslo, Norway.
4
Department of Gastroenterology, Oslo University Hospital-Rikshospitalet, 0372, Oslo, Norway.
5
K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo, 0424, Oslo, Norway. l.m.sollid@medisin.uio.no.
6
Department of Immunology, University of Oslo and Oslo University Hospital- Rikshospitalet, 0372, Oslo, Norway. l.m.sollid@medisin.uio.no.

Abstract

A hallmark of celiac disease (CeD), a chronic condition driven by cereal gluten exposure, is increase of gut intraepithelial γδ T cells. This may indicate pathogenic involvement of γδ T cells and existence of disease-specific γδ T-cell receptors (TCRs) recognizing defined antigen(s). We performed high-throughput and paired γδ TCR sequencing of single intraepithelial γδ T cells of untreated CeD patients (n = 8; 1821 cells), CeD patients treated with a gluten-free diet (n = 5; 436 cells) and controls (n = 7; 1068 cells). We found that CeD patients, both untreated and treated, had larger and more diverse γδ TCR repertoires, more frequent usage of TRDV1 and TRDV3 and different patterns of TCRγ/TCRδ-pairing compared with controls. Although we observed no public CDR3δ sequences, there were several public CDR3γ sequences-many of which were shared by not only the CeD patients, but also by the controls. These public CDR3s were characterized by few N/P nucleotide insertions with germline and near-germline configuration, hence being easy to generate. Previous findings of CeD-specific CDR3 motifs were not replicated. Thus, being unable to raise evidence for CeD-specific γδ TCRs in this first large, paired γδ TCR single-cell sequencing study, we project challenges for identification of CeD-relevant γδ TCR ligands.

PMID:
31728027
DOI:
10.1038/s41385-019-0222-9

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