title: Naive CD8⁺ T-cell precursors display structured TCR repertoires and composite antigen-driven selection dynamics.
abstract: Basic parameters of the naive antigen (Ag)-specific T-cell repertoire in humans remain poorly defined. Systematic characterization of this 'ground state' immunity in comparison with memory will allow a better understanding of clonal selection during immune challenge. Here, we used high-definition cell isolation from umbilical cord blood samples to establish the baseline frequency, phenotype and T-cell antigen receptor (TCR) repertoire of CD8(+) T-cell precursor populations specific for a range of viral and self-derived Ags. Across the board, these precursor populations were phenotypically naive and occurred with hierarchical frequencies clustered by Ag specificity. The corresponding patterns of TCR architecture were highly ordered and displayed partial overlap with adult memory, indicating biased structuring of the T-cell repertoire during Ag-driven selection. Collectively, these results provide new insights into the complex nature and dynamics of the naive T-cell compartment.
authors: Human Immunity Laboratory, Cellular Immunology Laboratory and Tumour Immunology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors: Michelle A
authors: MA
authors: Neller
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors: Kristin
authors: K
authors: Ladell
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors: James E
authors: JE
authors: McLaren
authors: Human Immunity Laboratory, Cellular Immunology Laboratory and Tumour Immunology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors: Katherine K
authors: KK
authors: Matthews
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors: Emma
authors: E
authors: Gostick
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors: Johanne M
authors: JM
authors: Pentier
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors: Garry
authors: G
authors: Dolton
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors: Andrea J A
authors: AJ
authors: Schauenburg
authors: Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Dan
authors: D
authors: Koning
authors: Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Ana Isabel C A
authors: AI
authors: Fontaine Costa
authors: Human Immunity Laboratory, Cellular Immunology Laboratory and Tumour Immunology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors: Thomas S
authors: TS
authors: Watkins
authors: Computational Biology Unit, Centre for Vascular Research, University of New South Wales, Kensington, NSW, Australia.
authors: Vanessa
authors: V
authors: Venturi
authors: Human Immunity Laboratory, Cellular Immunology Laboratory and Tumour Immunology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors: Corey
authors: C
authors: Smith
authors: Human Immunity Laboratory, Cellular Immunology Laboratory and Tumour Immunology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors: Rajiv
authors: R
authors: Khanna
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors: Kelly
authors: K
authors: Miners
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors: Mathew
authors: M
authors: Clement
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors: Linda
authors: L
authors: Wooldridge
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors: David K
authors: DK
authors: Cole
authors: Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Debbie
authors: D
authors: van Baarle
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors: Andrew K
authors: AK
authors: Sewell
authors: 1] Human Immunity Laboratory, Cellular Immunology Laboratory and Tumour Immunology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia [2] School of Medicine, The University of Queensland, Brisbane, QLD, Australia.
authors: Scott R
authors: SR
authors: Burrows
authors: 1] Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK [2] Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: David A
authors: DA
authors: Price
authors: 1] Human Immunity Laboratory, Cellular Immunology Laboratory and Tumour Immunology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia [2] Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK [3] School of Medicine, The University of Queensland, Brisbane, QLD, Australia.
authors: John J
authors: JJ
authors: Miles
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D060966:Clonal Selection, Antigen-Mediated; D000069439:Dasatinib / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D018189:Immunomagnetic Separation; D016130:Immunophenotyping; D007231:Infant, Newborn; D010446:Peptide Fragments / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D037182:T-Cell Antigen Receptor Specificity; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D001324:Autoantigens; D006680:HLA Antigens; D010446:Peptide Fragments; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D000069439:Dasatinib