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
Affiliations
Linda Voogd
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands; Corresponding author
Anne M.H.F. Drittij
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
Calinda K.E. Dingenouts
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
Kees L.M.C. Franken
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
Vincent van Unen
Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Palo Alto, CA, USA
Krista E. van Meijgaarden
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
Paula Ruibal
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
Renate S. Hagedoorn
Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands
Judith A. Leitner
Centre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
Peter Steinberger
Centre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
Mirjam H.M. Heemskerk
Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands
Mark M. Davis
Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Palo Alto, CA, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Palo Alto, CA, USA
Thomas J. Scriba
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
Tom H.M. Ottenhoff
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
Simone A. Joosten
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
Summary: 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.
