Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in highly public receptors.

Abstract:

BACKGROUND:The adaptive immune system maintains a diversity of T cells capable of recognizing a broad array of antigens. Each T cell's specificity for antigens is determined by its T cell receptors (TCRs), which together across all T cells form a repertoire of millions of unique receptors in each individual. Although many studies have examined how TCR repertoires change in response to disease or drugs, few have explored the temporal dynamics of the TCR repertoire in healthy individuals. RESULTS:Here we report immunosequencing of TCR β chains (TCRβ) from the blood of three healthy individuals at eight time points over one year. TCRβ repertoires of all peripheral-blood T cells and sorted memory T cells clustered clearly by individual, systematically demonstrating that TCRβ repertoires are specific to individuals across time. This individuality was absent from TCRβs from naive T cells, suggesting that the differences resulted from an individual's antigen exposure history, not genetic background. Many characteristics of the TCRβ repertoire (e.g., diversity, clonality) were stable across time, although we found evidence of T cell expansion dynamics even within healthy individuals. We further identified a subset of "persistent" TCRβs present across all time points. These receptors were rich in clonal and highly public receptors and may play a key role in immune system maintenance. CONCLUSIONS:Our results highlight the importance of longitudinal sampling of the immune system, providing a much-needed baseline for TCRβ dynamics in healthy individuals. Such a baseline will improve interpretation of changes in the TCRβ repertoire during disease or treatment.

journal_name

BMC Immunol

journal_title

BMC immunology

authors

Chu ND,Bi HS,Emerson RO,Sherwood AM,Birnbaum ME,Robins HS,Alm EJ

doi

10.1186/s12865-019-0300-5

subject

Has Abstract

pub_date

2019-06-21 00:00:00

pages

19

issue

1

issn

1471-2172

pii

10.1186/s12865-019-0300-5

journal_volume

20

pub_type

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