TCR deep sequencing of transgenic RAG-1-deficient mice reveals endogenous TCR recombination: a cause for caution.

Autor: McGuire HM; Centenary Institute, Camperdown, NSW, Australia.; Discipline of Pathology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, NSW, Australia.; Ramaciotti Facility for Human Systems Biology, Charles Perkins Centre, University of Sydney, NSW, Australia., Watkins TS; Centre for Biodiscovery and Molecular Development of Therapeutics, AITHM, James Cook University, Cairns, QLD, Australia.; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia., Field M; Centre for Biodiscovery and Molecular Development of Therapeutics, AITHM, James Cook University, Cairns, QLD, Australia., Taylor S; Takara Bio USA, Inc., 1290 Terra Bella Ave, Mountain View, CA, USA., Yasuyama N; Takara Bio USA, Inc., 1290 Terra Bella Ave, Mountain View, CA, USA., Farmer A; Takara Bio USA, Inc., 1290 Terra Bella Ave, Mountain View, CA, USA., Miles JJ; Centre for Biodiscovery and Molecular Development of Therapeutics, AITHM, James Cook University, Cairns, QLD, Australia.; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK., Fazekas de St Groth B; Discipline of Pathology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, NSW, Australia.; Ramaciotti Facility for Human Systems Biology, Charles Perkins Centre, University of Sydney, NSW, Australia.
Jazyk: angličtina
Zdroj: Immunology and cell biology [Immunol Cell Biol] 2018 Jul; Vol. 96 (6), pp. 642-645. Date of Electronic Publication: 2018 Mar 24.
DOI: 10.1111/imcb.12033
Abstrakt: The utility of T-cell receptor (TCR) transgenic mice in medical research has been considerable, with applications ranging from basic biology all the way to translational and clinical investigations. Crossing of TCR transgenic mice with either recombination-activating gene (RAG)-1 or RAG-2 knockouts is frequently used to generate mice with a monoclonal T-cell repertoire. However, low level productive TCR rearrangement has been reported in RAG-deficient mice expressing transgenic TCRs. Using deep sequencing, we set out to directly examine and quantify the presence of these endogenous TCRs. Our demonstration that functional nontransgenic TCRs are present in nonmanipulated mice has wide reaching ramifications worthy of critical consideration.
(© 2018 Australasian Society for Immunology Inc.)
Databáze: MEDLINE