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Chronic lymphocytic leukemia

Restrictions in the T-cell repertoire of chronic lymphocytic leukemia: high-throughput immunoprofiling supports selection by shared antigenic elements

Leukemia volume 31, pages 1555–1561 (2017)Cite this article

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Abstract

Immunoglobulin (IG) gene repertoire restrictions strongly support antigen selection in the pathogenesis of chronic lymphocytic leukemia (CLL). Given the emerging multifarious interactions between CLL and bystander T cells, we sought to determine whether antigen(s) are also selecting T cells in CLL. We performed a large-scale, next-generation sequencing (NGS) study of the T-cell repertoire, focusing on major stereotyped subsets representing CLL subgroups with undisputed antigenic drive, but also included patients carrying non-subset IG rearrangements to seek for T-cell immunogenetic signatures ubiquitous in CLL. Considering the inherent limitations of NGS, we deployed bioinformatics algorithms for qualitative curation of T-cell receptor rearrangements, and included multiple types of controls. Overall, we document the clonal architecture of the T-cell repertoire in CLL. These T-cell clones persist and further expand overtime, and can be shared by different patients, most especially patients belonging to the same stereotyped subset. Notably, these shared clonotypes appear to be disease-specific, as they are found in neither public databases nor healthy controls. Altogether, these findings indicate that antigen drive likely underlies T-cell expansions in CLL and may be acting in a CLL subset-specific context. Whether these are the same antigens interacting with the malignant clone or tumor-derived antigens remains to be elucidated.

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Acknowledgements

Supported in part by H2020 ‘AEGLE, An analytics framework for integrated and personalized healthcare services in Europe’, by the EU; ‘MEDGENET, Medical Genomics and Epigenomics Network’ (No.692298) by the EU. Part of the work was carried out with the support of core facilities of CEITEC – Central European Institute of Technology under CEITEC – open access project, ID number LM2011020, funded by the Ministry of Education, Youth and Sports of the Czech Republic under the activity ‘Projects of major infrastructures for research, development and innovations’. PS and BV are financially supported by the Ministry of Education, Youth and Sports of the Czech Republic under the project CEITEC 2020 (LQ1601) and by the Horizon2020 Programme Twinning (MEDGENET/2016–2018/no.692298).

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Authors and Affiliations

  1. Institute of Applied Biosciences, CERTH, Thessaloniki, Greece

    A Vardi, E Vlachonikola, M Karypidou, E Stalika, K Gemenetzi, C Maramis, N Maglaveras, I Chouvarda, K Stamatopoulos & A Hadzidimitriou

  2. Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece

    A Vardi & A Anagnostopoulos

  3. Medical School, University of Crete, Heraklion, Greece

    A Vardi

  4. CEITEC, Masaryk University and University Hospital Brno, Brno, Czech Republic

    V Bikos & S Pospisilova

  5. Laboratory of Medical Informatics, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

    C Maramis, N Maglaveras & I Chouvarda

  6. Immunology and National Tissue Typing Center, General Hospital of Athens ‘G. Gennimatas’, Athens, Thessaloniki, Greece

    A Siorenta

  7. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

    K Stamatopoulos & A Hadzidimitriou

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  1. A Vardi
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Correspondence to K Stamatopoulos.

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Vardi, A., Vlachonikola, E., Karypidou, M. et al. Restrictions in the T-cell repertoire of chronic lymphocytic leukemia: high-throughput immunoprofiling supports selection by shared antigenic elements. Leukemia 31, 1555–1561 (2017). https://doi.org/10.1038/leu.2016.362

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