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: Michael J Clemente, Bartlomiej Przychodzen, Andres Jerez, Brittney E Dienes, Manuel G Afable, Holleh Husseinzadeh, Hanna L M Rajala, Marcin W Wlodarski, Satu Mustjoki, Jaroslaw P Maciejewski
• Journal: Blood (Blood) Vol. 122 Issue 25 Pg. 4077-85 (Dec 12 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 24149287 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Complementarity Determining Regions
• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• CD8-Positive T-Lymphocytes
• Complementarity Determining Regions (genetics)
• Female
• Humans
• Leukemia, Large Granular Lymphocytic (genetics, pathology)
• Male
• Middle Aged
• Receptors, Antigen, T-Cell, alpha-beta (genetics)