Abundant cytomegalovirus (CMV) reactive clonotypes in the CD8(+) T cell receptor alpha repertoire following allogeneic transplantation

Clinical and Experimental Immunology
C S LinkE Bonifacio

Abstract

Allogeneic stem cell transplantation is potentially curative, but associated with post-transplantation complications, including cytomegalovirus (CMV) infections. An effective immune response requires T cells recognizing CMV epitopes via their T cell receptors (TCRs). Little is known about the TCR repertoire, in particular the TCR-α repertoire and its clinical relevance in patients following stem cell transplantation. Using next-generation sequencing we examined the TCR-α repertoire of CD8(+) T cells and CMV-specific CD8(+) T cells in four patients. Additionally, we performed single-cell TCR-αβ sequencing of CMV-specific CD8(+) T cells. The TCR-α composition of human leucocyte antigen (HLA)-A*0201 CMVpp65- and CMVIE -specific T cells was oligoclonal and defined by few dominant clonotypes. Frequencies of single clonotypes reached up to 11% of all CD8(+) T cells and half of the total CD8(+) T cell repertoire was dominated by few CMV-reactive clonotypes. Some TCR-α clonotypes were shared between patients. Gene expression of the circulating CMV-specific CD8(+) T cells was consistent with chronically activated effector memory T cells. The CD8(+) T cell response to CMV reactivation resulted in an expansion of a few TCR-α clonotypes to...Continue Reading

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Citations

Nov 5, 2016·European Journal of Immunology·Meriem Attaf, Andrew K Sewell
Mar 3, 2017·Nature Structural & Molecular Biology·InYoung SongLawrence J Stern
Mar 9, 2017·British Journal of Haematology·Cornelia S LinkJohannes Schetelig
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Jun 21, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Justyna OgonekLothar Hambach
Jan 31, 2019·Annual Review of Immunology·Philip Bradley, Paul G Thomas
Jun 30, 2019·Transplant International : Official Journal of the European Society for Organ Transplantation·Anastasia MinervinaIlgar Mamedov
Feb 23, 2020·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Omid ShahEverett H Meyer

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