LAUSR

Significance The human body detects foreign pathogens by T cells with specific receptors. These are not directly encoded in the genome but generated in a random process that combines small gene segments into functional subunits of the receptor. The β-chain of the T cell receptor is normally composed of three such gene segments. Here we identify a group of T cells that lack the middle segment in their receptor sequence. We find that such sequences are mostly generated before birth, persist over a human lifetime, and, as a result, are excessively shared between individuals. 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 TCRβ 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 TCRβ rearrangements lacking a D segment. Additionally, sequences without a D segment are more likely to be abundant within individuals and/or shared between individuals. Our analysis indicates that such sequences are preferentially generated during fetal development and persist within the elderly. Summarizing, TCRβ rearrangements without a D segment are not uncommon, and tend to allow for TCRβ chains with a high abundance in the naive repertoire.