title: TCRβ repertoire of CD4+ and CD8+ T cells is distinct in richness, distribution, and CDR3 amino acid composition.
abstract: The TCR repertoire serves as a reservoir of TCRs for recognizing all potential pathogens. Two major types of T cells, CD4(+) and CD8(+), that use the same genetic elements and process to generate a functional TCR differ in their recognition of peptide bound to MHC class II and I, respectively. However, it is currently unclear to what extent the TCR repertoire of CD4(+) and CD8(+) T cells is different. Here, we report a comparative analysis of the TCRβ repertoires of CD4(+) and CD8(+) T cells by use of a 5' rapid amplification of cDNA ends-PCR-sequencing method. We found that TCRβ richness of CD4(+) T cells ranges from 1.2 to 9.8 × 10(4) and is approximately 5 times greater, on average, than that of CD8(+) T cells in each study subject. Furthermore, there was little overlap in TCRβ sequences between CD4(+) (0.3%) and CD8(+) (1.3%) T cells. Further analysis showed that CD4(+) and CD8(+) T cells exhibited distinct preferences for certain amino acids in the CDR3, and this was confirmed further by a support vector machine classifier, suggesting that there are distinct and discernible differences between TCRβ CDR3 in CD4(+) and CD8(+) T cells. Finally, we identified 5-12% of the unique TCRβs that share an identical CDR3 with different variable genes. Together, our findings reveal the distinct features of the TCRβ repertoire between CD4(+) and CD8(+) T cells and could potentially be used to evaluate the competency of T cell immunity.
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Hoi Ming
authors.initials: HM
authors.lastname: Li
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Toyoko
authors.initials: T
authors.lastname: Hiroi
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Alvin
authors.initials: A
authors.lastname: Shi
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Guobing
authors.initials: G
authors.lastname: Chen
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Supriyo
authors.initials: S
authors.lastname: De
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: E Jeffrey
authors.initials: EJ
authors.lastname: Metter
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Wood
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Alexei
authors.initials: A
authors.lastname: Sharov
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Milner
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhan
authors.affiliation: Laboratories of *Molecular Biology and Immunology and Genetics, Gene Expression and Genomics and Bioinformatics Units, and Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA wengn@mail.nih.gov.
authors.forename: Nan-ping
authors.initials: NP
authors.lastname: Weng
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000032:analysis*; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000737:chemistry
chemical_list: D000596:Amino Acids; D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: Human; RACE; RNAseq; TCR diversity; supervised learning