Mtb HLA-E-tetramer-sorted CD8 + T cells have a diverse TCR repertoire.
Autor: | Voogd L; Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands., Drittij AMHF; Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands., Dingenouts CKE; Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands., Franken KLMC; Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands., Unen VV; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Palo Alto, CA, USA., van Meijgaarden KE; Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands., Ruibal P; Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands., Hagedoorn RS; Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands., Leitner JA; Centre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria., Steinberger P; Centre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria., Heemskerk MHM; Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands., Davis MM; 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., Scriba TJ; 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., Ottenhoff THM; Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands., Joosten SA; Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. |
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Jazyk: | angličtina |
Zdroj: | IScience [iScience] 2024 Feb 15; Vol. 27 (3), pp. 109233. Date of Electronic Publication: 2024 Feb 15 (Print Publication: 2024). |
DOI: | 10.1016/j.isci.2024.109233 |
Abstrakt: | 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. Competing Interests: The authors declare that they have no competing interest. (© 2024 The Author(s).) |
Databáze: | MEDLINE |
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