Invariant γδTCR natural killer-like effector T cells in the naked mole-rat

Guillem Sanchez Sanchez, Stephan Emmrich, Maria Georga, Ariadni Papadaki, Sofia Kossida, Andrei Seluanov, Vera Gorbunova and David Vermijlen ()
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Guillem Sanchez Sanchez: Université Libre de Bruxelles (ULB)
Stephan Emmrich: University of Rochester
Maria Georga: Université de Montpellier (UM)
Ariadni Papadaki: Université de Montpellier (UM)
Sofia Kossida: Université de Montpellier (UM)
Andrei Seluanov: University of Rochester
Vera Gorbunova: University of Rochester
David Vermijlen: Université Libre de Bruxelles (ULB)

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract The naked mole-rat (Heterocephalus glaber) is a long-lived rodent species showing resistance to the development of cancer. Although naked mole-rats have been reported to lack natural killer (NK) cells, γδ T cell-based immunity has been suggested in this species, which could represent an important arm of the immune system for antitumor responses. Here, we investigate the biology of these unconventional T cells in peripheral tissues (blood, spleen) and thymus of the naked mole-rat at different ages by TCR repertoire profiling and single-cell gene expression analysis. Using our own TCR annotation in the naked mole-rat genome, we report that the γδ TCR repertoire is dominated by a public invariant Vγ4-2/Vδ1-4 TCR, containing the complementary-determining-region-3 (CDR3)γ CTYWDSNYAKKLF / CDR3δ CALWELRTGGITAQLVF that are likely generated by short-homology-repeat-driven DNA rearrangements. This invariant TCR is specifically found in γδ T cells expressing genes associated with NK cytotoxicity and is generated in both the thoracic and cervical thymus of the naked mole-rat until adult life. Our results indicate that invariant Vγ4-2/Vδ1-4 NK-like effector T cells in the naked mole-rat can contribute to tumor immunosurveillance by γδ TCR-mediated recognition of a common molecular signal.

Date: 2024
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DOI: 10.1038/s41467-024-48652-z

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