Mtb HLA-E-tetramer-sorted CD8+ T cells have a diverse TCR repertoire

Linda Voogd; Anne M H F Drittij; Calinda K E Dingenouts; Kees L M C Franken; Vincent van Unen; Krista E van Meijgaarden; Paula Ruibal; Renate S Hagedoorn; Judith A Leitner; Peter Steinberger; Mirjam H M Heemskerk; Mark M Davis; Thomas J Scriba; Tom H M Ottenhoff; Simone A Joosten

doi:10.1016/j.isci.2024.109233

Mtb HLA-E-tetramer-sorted CD8⁺ T cells have a diverse TCR repertoire

iScience. 2024 Feb 15;27(3):109233. doi: 10.1016/j.isci.2024.109233. eCollection 2024 Mar 15.

Authors

Linda Voogd¹, Anne M H F Drittij¹, Calinda K E Dingenouts¹, Kees L M C Franken¹, Vincent van Unen², Krista E van Meijgaarden¹, Paula Ruibal¹, Renate S Hagedoorn³, Judith A Leitner⁴, Peter Steinberger⁴, Mirjam H M Heemskerk³, Mark M Davis^{2

5}, Thomas J Scriba⁶, Tom H M Ottenhoff¹, Simone A Joosten¹

Affiliations

¹ Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands.
² Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Palo Alto, CA, USA.
³ Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.
⁴ Centre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria.
⁵ Howard Hughes Medical Institute, Stanford University School of Medicine, Palo Alto, CA, USA.
⁶ South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

Abstract

HLA-E molecules can present self- and pathogen-derived peptides to both natural killer (NK) cells and T cells. T cells that recognize HLA-E peptides via their T cell receptor (TCR) are termed donor-unrestricted T cells due to restricted allelic variation of HLA-E. The composition and repertoire of HLA-E TCRs is not known so far. We performed TCR sequencing on CD8⁺ T cells from 21 individuals recognizing HLA-E tetramers (TMs) folded with two Mtb-HLA-E-restricted peptides. We sorted HLA-E Mtb TM⁺ and TM^- CD8⁺ T cells directly ex vivo and performed bulk RNA-sequencing and single-cell TCR sequencing. The identified TCR repertoire was diverse and showed no conservation between and within individuals. TCRs selected from our single-cell TCR sequencing data could be activated upon HLA-E/peptide stimulation, although not robust, reflecting potentially weak interactions between HLA-E peptide complexes and TCRs. Thus, HLA-E-Mtb-specific T cells have a highly diverse TCR repertoire.

Keywords: Genotyping; Immunology; Transcriptomics.

Abstract

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