High Frequency of Shared Clonotypes in Human T Cell Receptor Repertoires

• Published in: Cell reports (Cambridge) Vol. 32; no. 2; p. 107882
• Main Authors: Soto, Cinque, Bombardi, Robin G., Kozhevnikov, Morgan, Sinkovits, Robert S., Chen, Elaine C., Branchizio, Andre, Kose, Nurgun, Day, Samuel B., Pilkinton, Mark, Gujral, Madhusudan, Mallal, Simon, Crowe, James E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.07.2020; Elsevier
• Subjects: adaptive immunity; Adult; Amino Acid Sequence; CDR3; Clone Cells - metabolism; clonotypes; DNA - genetics; Female; Genome, Human; HLA; Humans; immune repertoire sequencing; Lymphocyte Subsets - immunology; Male; Middle Aged; Receptors, Antigen, T-Cell, alpha-beta - chemistry; Receptors, Antigen, T-Cell, alpha-beta - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; TCR; Young Adult; clonotypes; TCR; HLA; immune repertoire sequencing; CDR3; adaptive immunity
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.107882

The collection of T cell receptors (TCRs) generated by somatic recombination is large but unknown. We generate large TCR repertoire datasets as a resource to facilitate detailed studies of the role of TCR clonotypes and repertoires in health and disease. We estimate the size of individual human recombined and expressed TCRs by sequence analysis and determine the extent of sharing between individual repertoires. Our experiments reveal that each blood sample contains between 5 million and 21 million TCR clonotypes. Three individuals share 8% of TCRβ- or 11% of TCRα-chain clonotypes. Sorting by T cell phenotypes in four individuals shows that 5% of naive CD4+ and 3.5% of naive CD8+ subsets share their TCRβ clonotypes, whereas memory CD4+ and CD8+ subsets share 2.3% and 0.4% of their clonotypes, respectively. We identify the sequences of these shared TCR clonotypes that are of interest for studies of human T cell biology. [Display omitted] •TCR clonotype sharing between individuals is higher than expected by chance•High-frequency TCR clonotypes are captured using gDNA and mRNA sequencing methods•Shared TCR clonotypes have a higher probability of being generated•Functional annotation for TCR clonotypes can be obtained using GenBank Soto et al. examine the extent to which five healthy adults share their T cell receptor (TCR) repertoire. Using sequencing and bioinformatics, they show a high prevalence of shared clonotypes even considering different T cell phenotypes. Possible functions for some clonotypes are inferred based on homology with TCRs in GenBank.