title: Lack of common TCRA and TCRB clonotypes in CD8(+)/TCRαβ(+) T-cell large granular lymphocyte leukemia: a review on the role of antigenic selection in the immunopathogenesis of CD8(+) T-LGL.
abstract: Clonal CD8(+)/T-cell receptor (TCR)αβ(+) T-cell large granular lymphocyte (T-LGL) proliferations constitute the most common subtype of T-LGL leukemia. Although the etiology of T-LGL leukemia is largely unknown, it has been hypothesized that chronic antigenic stimulation contributes to the pathogenesis of this disorder. In the present study, we explored the association between expanded TCR-Vβ and TCR-Vα clonotypes in a cohort of 26 CD8(+)/TCRαβ(+) T-LGL leukemia patients, in conjunction with the HLA-ABC genotype, to find indications for common antigenic stimuli. In addition, we applied purpose-built sophisticated computational tools for an in-depth evaluation of clustering of TCRβ (TCRB) complementarity determining region 3 (CDR3) amino-acid LGL clonotypes. We observed a lack of clear TCRA and TCRB CDR3 homology in CD8(+)/TCRαβ(+) T-LGL, with only low level similarity between small numbers of cases. This is in strong contrast to the homology that is seen in CD4(+)/TCRαβ(+) T-LGL and TCRγδ(+) T-LGL and thus underlines the idea that the LGL types have different etiopathogenesis. The heterogeneity of clonal CD8(+)/TCRαβ(+) T-LGL proliferations might in fact suggest that multiple pathogens or autoantigens are involved.
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: Sandberg
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kallemeijn
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: W A
authors.initials: WA
authors.lastname: Dik
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Tielemans
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: I L M
authors.initials: IL
authors.lastname: Wolvers-Tettero
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: van Gastel-Mol
authors.affiliation: 1] Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands [2] Department of Pediatric Hematology and Oncology, Medical University of Silesia, Zabrze, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Szczepanski
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: Pol
authors.affiliation: Institute of Agrobiotechnology, Center for Research and Technology Hellas, Thessaloniki, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Darzentas
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: J J M
authors.initials: JJ
authors.lastname: van Dongen
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: A W
authors.initials: AW
authors.lastname: Langerak