title: Discovery of invariant T cells by next-generation sequencing of the human TCR α-chain repertoire.
abstract: During infection and autoimmune disease, activation and expansion of T cells take place. Consequently, the TCR repertoire contains information about ongoing and past diseases. Analysis and interpretation of the human TCR repertoire are hampered by its size and stochastic variation and by the diversity of Ags and Ag-presenting molecules encoded by the MHC, but are highly desirable and would greatly impact fundamental and clinical immunology. A subset of the TCR repertoire is formed by invariant T cells. Invariant T cells express interdonor-conserved TCRs and recognize a limited set of Ags, presented by nonpolymorphic Ag-presenting molecules. Discovery of the three known invariant T cell populations has been a tedious and slow process, identifying them one by one. Because conservation of the TCR α-chain of invariant T cells is much higher than the β-chain, and because the TCR α-chain V gene segment TRAV1-2 is used by two of the three known invariant TCRs, we employed next-generation sequencing of TCR α-chains that contain the TRAV1-2 gene segment to identify 16 invariant TCRs shared among many blood donors. Frequency analysis of individual clones indicates these T cells are expanded in many donors, implying an important role in human immunity. This approach extends the number of known interdonor-conserved TCRs and suggests that many more exist and that these TCR patterns can be used to systematically evaluate human Ag exposure.
authors.affiliation: Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, the Netherlands;
authors.forename: Barbera
authors.initials: B
authors.lastname: van Schaik
authors.affiliation: Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, the Netherlands; Laboratory for Genome Analysis, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, the Netherlands;
authors.forename: Paul
authors.initials: P
authors.lastname: Klarenbeek
authors.affiliation: Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, the Netherlands; Laboratory for Genome Analysis, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, the Netherlands;
authors.forename: Marieke
authors.initials: M
authors.lastname: Doorenspleet
authors.affiliation: Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, the Netherlands;
authors.forename: Antoine
authors.initials: A
authors.lastname: van Kampen
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; and.
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
authors.affiliation: Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, the Netherlands; Laboratory for Genome Analysis, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, the Netherlands;
authors.forename: Niek
authors.initials: N
authors.lastname: de Vries
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; and Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, the Netherlands i.vanrhijn@uu.nl.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Van Rhijn
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D058070:Asymptomatic Diseases; D001483:Base Sequence; D002999:Clone Cells; D017124:Conserved Sequence; D005260:Female; D015870:Gene Expression; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016130:Immunophenotyping; D055985:Latent Tuberculosis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D006680:HLA Antigens; D020033:Protein Isoforms; D016693:Receptors, Antigen, T-Cell, alpha-beta