RT Journal Article
SR Electronic
T1 Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in public receptors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 262667
DO 10.1101/262667
A1 Nathaniel D. Chu
A1 Haixin Sarah Bi
A1 Ryan O. Emerson
A1 Anna M. Sherwood
A1 Michael E. Birnbaum
A1 Harlan S. Robins
A1 Eric J. Alm
YR 2018
UL http://biorxiv.org/content/early/2018/02/08/262667.abstract
AB Background The adaptive immune system maintains a diversity of T cells capable of recognizing a broad array of antigens. Each T cell’s specificity and affinity for antigens is determined by its T cell receptors (TCRs), which together across all T cells form a repertoire of tens 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 from samples of all T cells and memory T cells clearly clustered by individual, confirming that TCRβ repertoires are specific to individuals across time. This individuality was absent from TCRβs from naive T cells, suggesting that these differences result from an individual’s antigen exposure history. Many characteristics of the TCRβ repertoire (e.g., alpha 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, and these receptors were rich in clonal and public receptors.Conclusions Our results revealed persistent receptors that may play a key role in immune system maintenance. They further highlight the importance of longitudinal sampling of the immune system and provide a much-needed baseline for TCRβ dynamics in healthy individuals. Such a baseline should help improve interpretation of changes in the TCRβ repertoire during disease or treatment.