The naive T-cell receptor repertoire has an extremely broad distribution of clone sizes.
Adaptive Immunity
Algorithms
Antigens
/ immunology
Clonal Evolution
/ genetics
Computational Biology
/ methods
High-Throughput Nucleotide Sequencing
Humans
Immunologic Memory
Models, Biological
Organ Specificity
/ genetics
Receptors, Antigen, T-Cell
/ genetics
Receptors, Antigen, T-Cell, alpha-beta
/ genetics
T-Lymphocyte Subsets
/ immunology
T-Lymphocytes
/ immunology
V(D)J Recombination
bioinformatics
computational biology
human
immunology
inflammation
modelling
repertoire sequencing
systems biology
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
18 03 2020
18 03 2020
Historique:
received:
03
07
2019
accepted:
03
03
2020
entrez:
19
3
2020
pubmed:
19
3
2020
medline:
31
3
2021
Statut:
epublish
Résumé
The clone size distribution of the human naive T-cell receptor (TCR) repertoire is an important determinant of adaptive immunity. We estimated the abundance of TCR sequences in samples of naive T cells from blood using an accurate quantitative sequencing protocol. We observe most TCR sequences only once, consistent with the enormous diversity of the repertoire. However, a substantial number of sequences were observed multiple times. We detect abundant TCR sequences even after exclusion of methodological confounders such as sort contamination, and multiple mRNA sampling from the same cell. By combining experimental data with predictions from models we describe two mechanisms contributing to TCR sequence abundance. TCRα abundant sequences can be primarily attributed to many identical recombination events in different cells, while abundant TCRβ sequences are primarily derived from large clones, which make up a small percentage of the naive repertoire, and could be established early in the development of the T-cell repertoire.
Identifiants
pubmed: 32187010
doi: 10.7554/eLife.49900
pii: 49900
pmc: PMC7080410
doi:
pii:
Substances chimiques
Antigens
0
Receptors, Antigen, T-Cell
0
Receptors, Antigen, T-Cell, alpha-beta
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek
ID : 22.005.023
Organisme : Netherlands Genomics Initiative
ID : FES0908
Informations de copyright
© 2020, de Greef et al.
Déclaration de conflit d'intérêts
Pd, TO, BG, MI, JH, RH, BC, Rd No competing interests declared
Références
Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19414-9
pubmed: 20974936
Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):3974-3981
pubmed: 30765525
Nature. 1988 Aug 4;334(6181):395-402
pubmed: 3043226
J Clin Invest. 2013 Feb;123(2):594-9
pubmed: 23281401
Front Immunol. 2013 Nov 11;4:366
pubmed: 24273540
PLoS Comput Biol. 2017 Jul 6;13(7):e1005572
pubmed: 28683116
J Theor Biol. 2008 Nov 21;255(2):237-49
pubmed: 18692074
J Exp Med. 1997 Oct 6;186(7):1149-58
pubmed: 9314563
Science. 1999 Oct 29;286(5441):958-61
pubmed: 10542151
Scand J Immunol. 1985 Nov;22(5):563-75
pubmed: 4081647
J Theor Biol. 1994 Aug 21;169(4):375-90
pubmed: 7967629
PLoS Biol. 2018 Apr 11;16(4):e2003949
pubmed: 29641514
J Immunol. 2011 Apr 1;186(7):4285-94
pubmed: 21383244
Sci Transl Med. 2015 Apr 8;7(282):282ra48
pubmed: 25855494
Methods Mol Biol. 2019;1884:15-42
pubmed: 30465193
Adv Immunol. 1999;73:301-27
pubmed: 10399009
Blood. 2009 Nov 5;114(19):4099-107
pubmed: 19706884
Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13694-9
pubmed: 21813761
J Exp Med. 2013 Oct 21;210(11):2305-20
pubmed: 24101382
Immunol Today. 1998 Sep;19(9):395-404
pubmed: 9745202
Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9875-80
pubmed: 24941953
Nat Rev Immunol. 2004 Feb;4(2):123-32
pubmed: 15040585
Bioinformatics. 2016 Oct 15;32(20):3098-3106
pubmed: 27324198
Nat Commun. 2018 Feb 8;9(1):561
pubmed: 29422654
Mol Immunol. 2017 May;85:66-80
pubmed: 28212502
PLoS Comput Biol. 2019 Mar 4;15(3):e1006874
pubmed: 30830899
Nucleic Acids Res. 2018 Jan 4;46(D1):D419-D427
pubmed: 28977646
J Immunol. 2014 Mar 1;192(5):2143-55
pubmed: 24501199
Bioinformatics. 2013 Mar 1;29(5):542-50
pubmed: 23303508
Annu Rev Immunol. 2010;28:275-94
pubmed: 20307209
Front Immunol. 2013 Dec 26;4:485
pubmed: 24421780
Front Immunol. 2017 Oct 12;8:1267
pubmed: 29075258
Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):532-540
pubmed: 31879353
Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21432-7
pubmed: 23236163
Proc Natl Acad Sci U S A. 2015 Dec 15;112(50):E6917-26
pubmed: 26607449
Immunol Cell Biol. 2009 Aug-Sep;87(6):445-56
pubmed: 19290017
Immunol Rev. 2018 Jul;284(1):167-179
pubmed: 29944757
Aging Cell. 2015 Apr;14(2):219-27
pubmed: 25627171
J Theor Biol. 2010 Aug 7;265(3):396-410
pubmed: 20471403
Science. 1997 Jun 27;276(5321):2057-62
pubmed: 9197272
Nat Commun. 2014 May 15;5:3866
pubmed: 24832684
Nat Rev Immunol. 2009 Dec;9(12):823-32
pubmed: 19935802
Immunity. 2012 Feb 24;36(2):288-97
pubmed: 22365666
Nat Med. 2011 Sep 18;17(10):1290-7
pubmed: 21926977
Nat Genet. 2017 May;49(5):659-665
pubmed: 28369038
Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16161-6
pubmed: 22988065
Nat Protoc. 2013 Jan;8(1):33-42
pubmed: 23222456
Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):274-9
pubmed: 26711994
Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13139-44
pubmed: 25157137
Nat Immunol. 2016 Aug;17(8):966-75
pubmed: 27270402
Immunity. 2018 Feb 20;48(2):202-213
pubmed: 29466753
Immunity. 2015 Nov 17;43(5):859-69
pubmed: 26522985
Nat Rev Immunol. 2012 Sep;12(9):669-77
pubmed: 22918468
J Exp Med. 1994 Sep 1;180(3):1171-6
pubmed: 8064234
Sci Transl Med. 2010 Sep 1;2(47):47ra64
pubmed: 20811043
J Theor Biol. 2016 Jan 21;389:214-24
pubmed: 26546971