Lack of common TCRA and TCRB clonotypes in CD8(+)/TCR alpha beta(+) T-cell large granular lymphocyte leukemia: a review on the role of antigenic selection in the immunopathogenesis of CD8(+) T-LGL

Yorick Sandberg, Martine Kallemeijn, Wim Dik, Dennis Tielemans, Ingrid Tettero, Ellen Mol, Tomek Szczepanski, Y (Y.) Pol, N Darzentas, Jacques Dongen, Ton Langerak

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Abstract

Clonal CD8(+)/T-cell receptor (TCR)alpha beta(+) 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-V beta and TCR-V alpha clonotypes in a cohort of 26 CD8(+)/TCR alpha beta(+) 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 TCR beta (TCRB) complementarity determining region 3 (CDR3) amino-acid LGL clonotypes. We observed a lack of clear TCRA and TCRB CDR3 homology in CD8(+)/TCR alpha beta(+) 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(+)/TCR alpha beta(+) T-LGL and TCR gamma delta(+) T-LGL and thus underlines the idea that the LGL types have different etiopathogenesis. The heterogeneity of clonal CD8(+)/TCR alpha beta(+) T-LGL proliferations might in fact suggest that multiple pathogens or autoantigens are involved.
Original languageUndefined/Unknown
JournalBlood Cancer Journal
Volume4
DOIs
Publication statusPublished - 2014

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