T cell receptor assessment in autoimmune disease requires access to the most adjacent immunologically active organ.
Next generation sequencing of T and B cell receptors is emerging as a valuable and effective method to diagnose and monitor hematopoietic malignancies. So far, this approach has not been fully explored in regard to autoimmune diseases. T cells develop in the thymus where they undergo positive and negative selection, and the autoimmune regulator (Aire) is central in the establishment of immunological tolerance. Loss of Aire leads to severe multiorgan autoimmune disease with infiltration of autoreactive T cells in affected organs. Here, we have utilized next generation sequencing technology to investigate the T cell receptor repertoire in autoimmunity induced by immunization of mice with a self-antigen, myeloperoxidase. By investigating the T cell receptor repertoire in peripheral blood, spleen and lumbar lymph nodes from naïve and immunized Aire -/- mice and wild type littermates, changes in the usage of V and J genes were evident. Our results identify TCR clonotypes which could be potential targets for immune therapy. Also, Aire -/- autoimmunity is driven by a variety of autoantigens where the autoimmune response is highly polyclonal, and access to the most adjacent immunologically active tissue is required to identify T cell receptor sequences that are potentially unique to the antigen in Aire-/- immunized mice.
Department of Genetics and Molecular Pathology, Centre for Cancer Biology, An Alliance Between SA Pathology and the University of South Australia, Adelaide, Australia; Department of Clinical Science, University of Bergen, Norway. Electronic address: Bergithe.oftedal@uib.no.
Bergithe E
BE
Oftedal
Department of Genetics and Molecular Pathology, Centre for Cancer Biology, An Alliance Between SA Pathology and the University of South Australia, Adelaide, Australia; Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden.
Brita
B
Ardesjö Lundgren
Adaptive Biotechnologies, 1551 Eastlake Ave E #200, Seattle, WA, 98102, USA.
David
D
Hamm
Centre for Inflammatory Diseases, Monash University Department of Medicine, Clayton, Australia.
Poh-Yi
PY
Gan
Centre for Inflammatory Diseases, Monash University Department of Medicine, Clayton, Australia.
Stephen R
SR
Holdsworth
Department of Genetics and Molecular Pathology, Centre for Cancer Biology, An Alliance Between SA Pathology and the University of South Australia, Adelaide, Australia; School of Medicine, University of Adelaide, Adelaide, Australia.
Christopher N
CN
Hahn
ACRF Cancer Genomics Facility, Centre for Cancer Biology, SA Pathology, Adelaide, Australia; School of Medicine, University of Adelaide, Adelaide, Australia.
Andreas W
AW
Schreiber
Department of Genetics and Molecular Pathology, Centre for Cancer Biology, An Alliance Between SA Pathology and the University of South Australia, Adelaide, Australia; ACRF Cancer Genomics Facility, Centre for Cancer Biology, SA Pathology, Adelaide, Australia; School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Australia; School of Biological Sciences, University of Adelaide, Australia; School of Medicine, University of Adelaide, Adelaide, Australia. Electronic address: hamish.scott@sa.gov.au.
Hamish S
HS
Scott
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics*; D002450:Cell Communication / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta
Autoimmune regulator; Next generation sequencing; T cell receptor repertoire