Biology subjects

Emerson, R. O.

Publications and source records attributed to Emerson, R. O..

2 recordsLinked to original sources

bioRxiv2018

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

BackgroundThe adaptive immune system maintains a diversity of T cells capable of recognizing a broad array of antigens. Each T cells 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.\n\nResultsHere we report immunosequencing of TCR {beta} chains (TCR{beta}) from the blood of three healthy individuals at eight time points over one year. TCR{beta} repertoires from samples of all T cells and memory T cells clearly clustered by individual, confirming that TCR{beta} repertoires are specific to individuals across time. This individuality was absent from TCR{beta}s from naive T cells, suggesting that these differences result from an individuals antigen exposure history. Many characteristics of the TCR{beta} 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\" TCR{beta}s present across all time points, and these receptors were rich in clonal and public receptors.\n\nConclusionsOur 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 TCR{beta} dynamics in healthy individuals. Such a baseline should help improve interpretation of changes in the TCR{beta} repertoire during disease or treatment.

immunology↗

bioRxiv2017

Unbiased Definition Of A Shared T-Cell Receptor Motif Enables Population-Based Studies Of Tuberculosis

Peptide-specific T cells that are restricted by highly polymorphic major histocompatibility complex (MHC) proteins express diverse T-cell receptors (TCRs) that are rarely shared among unrelated individuals. T-cells can also recognize bacterial lipid antigens that bind the relatively non-polymorphic CD1 family of proteins. However, genetic variation in human CD1 genes and TCR diversity expressed by CD1-restricted T-cells have not been quantitatively determined. Here, we show that CD1B is nearly nucleotide-identical across all five continental ancestry groups, providing evidence for purifying selection during human evolution. We used CD1B tetramers loaded with a mycobacterial glycolipid antigen to isolate T-cells from four genetically unrelated South African adults and cataloged thousands of TCRs from in-vitro expanded T-cells using immunosequencing. We identified highly conserved motifs that were co-expressed as a functional heterodimer and significantly enriched among tetramer-positive T-cells sorted directly from peripheral blood. Finally, we show that frequencies of these TCR motifs are increased in the blood of patients with active tuberculosis compared to uninfected controls, a finding that is confirmed by ex-vivo frequencies of tetramer-positive T-cells determined by flow cytometry. These data provide a framework for unbiased definition of TCRs targeting lipid antigens, which can be tested for clinical associations independently of host genetic background.\n\nBrief SummaryWe used human genetics and immunosequencing to define a shared T-cell receptor motif that is specific for a mycobacterial lipid antigen and associated with tuberculosis independently of host genetic background.

immunology↗