title: Deep sequencing of the T-cell receptor repertoire in CD8+ T-large granular lymphocyte leukemia identifies signature landscapes.
abstract: New massively parallel sequencing technology enables, through deep sequencing of rearranged T-cell receptor (TCR) Vβ complementarity-determining region 3 (CDR3) regions, a previously inaccessible level of TCR repertoire analysis. The CDR3 repertoire diversity reflects clonal composition, the potential antigenic recognition spectrum, and the quantity of available T-cell responses. In this context, T-large granular lymphocyte (T-LGL) leukemia is a chronic clonal lymphoproliferation of cytotoxic T cells often associated with autoimmune diseases and various cytopenias. Using CD8(+) T-LGL leukemia as a model disease, we set out to evaluate and compare the TCR deep-sequencing spectra of both patients and healthy controls to better understand how TCR deep sequencing could be used in the diagnosis and monitoring of not only T-LGL leukemia but also reactive processes such as autoimmune disease and infection. Our data demonstrate, with high resolution, significantly decreased diversity of the T-cell repertoire in CD8(+) T-LGL leukemia and suggest that many T-LGL clonotypes may be private to the disease and may not be present in the general public, even at the basal level.
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH;
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clemente
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Przychodzen
authors.forename: Andres
authors.initials: A
authors.lastname: Jerez
authors.forename: Brittney E
authors.initials: BE
authors.lastname: Dienes
authors.forename: Manuel G
authors.initials: MG
authors.lastname: Afable
authors.forename: Holleh
authors.initials: H
authors.lastname: Husseinzadeh
authors.forename: Hanna L M
authors.initials: HL
authors.lastname: Rajala
authors.forename: Marcin W
authors.initials: MW
authors.lastname: Wlodarski
authors.forename: Satu
authors.initials: S
authors.lastname: Mustjoki
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes; D022801:Complementarity Determining Regions / Q000235:genetics*; D005260:Female; D006801:Humans; D054066:Leukemia, Large Granular Lymphocytic / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
chemical_list: D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta