Biology subjects

de Greef, P. C.

Publications and source records attributed to de Greef, P. C..

3 recordsLinked to original sources

bioRxiv2023

Towards a robust comparison of diversity between sampled TCR repertoires

T-cell receptor (TCR) repertoire sequencing data provides quantitative insight into the distribution of T-cell clones. The diversity of the TCR repertoire in humans tends do decrease with age, which may be a key determinant explaining immune senescence in older individuals. To address this, we first analyze how the diversity of a potential T-cell response against an unseen pathogen changes with age. Next, we discuss the complications with interpreting the outcomes of such an analysis. Specifically, the changes in T-cell subset sizes confound analyses of TCR diversity, and typical sample sizes do not easily allow for a robust quantification of this diversity. Thus, explaining immune senescence as a result of decreasing TCR diversity is far from straightforward and requires a detailed, robust, and quantitative analysis.

immunology↗

bioRxiv2021

TCRβ rearrangements without D-segment are common, abundant and public

T cells play an important role in adaptive immunity. An enormous clonal diversity of T-cells with a different specificity, encoded by the T-cell receptor (TCR), protect the body against infection. Most TCR{beta} chains are generated from a V-, D-, and J-segment during recombination in the thymus. Although complete absence of the D-segment is not easily detectable from sequencing data, we find convincing evidence for a substantial proportion of TCR{beta} rearrangements lacking a D-segment. Additionally, sequences without a D-segment are more likely to be abundant within individuals and/or shared between individuals. We find that such sequences are preferentially generated during fetal development and persist within the elderly. Summarizing, TCR{beta} rearrangements without a D-segment are not uncommon, and tend to allow for TCR{beta} chains with a high abundance in the naive repertoire.

immunology↗

bioRxiv2019

The naive T-cell receptor repertoire has an extremely broad distribution of clone sizes

The human naive T-cell receptor (TCR) repertoire is extremely diverse and accurately estimating its distribution is challenging. We address this challenge by combining a quantitative sequencing protocol of TCRA and TCRB sequences with computational modelling. We observed the vast majority of TCR chains only once in our samples, confirming the enormous diversity of the naive repertoire. However, a substantial number of sequences were observed multiple times within samples, and we demonstrated that this is due to expression by many cells in the naive pool. We reason that and {beta} chains are frequently observed due to a combination of selective processes and summation over multiple clones expressing these chains. We test the contribution of both mechanisms by predicting samples from phenomenological and mechanistically modelled repertoire distributions. By comparing these with sequencing data, we show that frequently observed chains are likely to be derived from multiple clones. Still, a neutral model of T-cell homeostasis cannot account for the observed distributions. We conclude that the data are only compatible with distributions of many small clones in combination with a sufficient number of very large naive T-cell clones, the latter most likely as a result of peripheral selection.

immunology↗