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Illegitimate recombination between T cell receptor genes in humans and pigs (Sus scrofa domestica)

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Abstract

T cell receptor (TCR) genes (TRA/TRD, TRB and TRG) reside in three regions on human chromosomes (14q11.2, 7q34 and 7p14, respectively) and pig chromosomes (7q15.3-q21, 18q11.3-q12 and 9q21-22, respectively). During the maturation of T cells, TCR genes are rearranged by site-specific recombination. Occasionally, interlocus recombination of different TCR genes takes place, resulting in chromosome rearrangements. It has been suggested that the absolute number of these “innocent” trans-rearrangements correlates with the risk of lymphoma. The aims of this work were to assess the frequencies of rearrangements with breakpoints in TCR genes in domestic pig lymphocytes and to compare these with the frequencies of corresponding rearrangements in human lymphocytes by using fluorescence in situ hybridization with chromosome painting probes. We show that frequencies of trans-rearrangements involving TRA/TRD locus in pigs are significantly higher than the frequency of translocations with breakpoints in TRB and TRG genes in pigs and the frequencies of corresponding trans-rearrangements involving TRA/TRD locus in humans. Complex structure of the pig TRA/TRD locus with high number of potential V(D)J rearrangements compared to the human locus may account for the observed differences. Furthermore, we demonstrated that trans-rearrangements involving pig TRA/TRD locus occur at lower frequencies in γδ T cells than in αβ T lymphocytes. The decrease of the frequencies in γδ T cells is probably caused by the absence of TRA recombination during maturation of this T cell lineage. High numbers of innocent trans-rearrangements in pigs may indicate a higher risk of T-cell lymphoma than in humans.

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Abbreviations

BAC:

Bacterial artificial chromosome

FISH:

Fluorescence in situ hybridization

PBL:

Peripheral blood lymphocyte

PBMC:

Peripheral blood mononuclear cells

PHA:

Phytohaemagglutinin

PWM:

Pokeweed mitogen

TRA :

T cell receptor alpha locus

TRB :

T cell receptor beta locus

TRD :

T cell receptor delta locus

TRG :

T cell receptor gamma locus

TCR:

T cell receptor

VDJ:

Variable, diversity and joining

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Acknowledgments

This work was supported by the Grant Agency of the Czech Republic, project P502/12/1966, and the Central European Institute of Technology (ED1.1.00/02.0068) via the European Regional Development Fund. We would like to thank Lenka Leva for her technical help and Thuraya Awadova for her assistance with statistical analysis.

Conflict of interest

Petra Musilova, Jitka Drbalova, Svatava Kubickova, Halina Cernohorska, Hana Stepanova and Jiri Rubes declare that they have no conflict of interest.

Ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Authors and Affiliations

  1. Department of Genetics and Reproduction, Central European Institute of Technology-Veterinary Research Institute, Hudcova 70, 621 00, Brno, Czech Republic

    Petra Musilova, Jitka Drbalova, Svatava Kubickova, Halina Cernohorska & Jiri Rubes

  2. Department of Immunology, Veterinary Research Institute, Hudcova 70, 621 00, Brno, Czech Republic

    Hana Stepanova

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  1. Petra Musilova
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Correspondence to Petra Musilova.

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Responsible Editor: Matthew Breen.

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Musilova, P., Drbalova, J., Kubickova, S. et al. Illegitimate recombination between T cell receptor genes in humans and pigs (Sus scrofa domestica). Chromosome Res 22, 483–493 (2014). https://doi.org/10.1007/s10577-014-9434-8

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  • DOI: https://doi.org/10.1007/s10577-014-9434-8

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