T-cell receptor αβ chain pairing is associated with CD4 + and CD8 + lineage specification

Abstract While a highly diverse T-cell receptor (TCR) repertoire is the hallmark of a healthy adaptive immune system, relatively little is understood about how the CD4 + and CD8 + TCR repertoires differ from one another. We here utilize high-throughput single T-cell sequencing to obtain approximately 100,000 TCR αβ chain pairs from human subjects, stratified into CD4 + and CD8 + lineages. We reveal that substantial information about T-cell lineage is encoded by V αβ gene pairs and, to a lesser extent, by several other TCR features such as CDR3 length and charge. We further find that the strength of association between the β chain and T-cell lineage is surprisingly weak, similar in strength to that of the α chain. Using machine learning classifiers to predict T-cell lineage from TCR features, we demon-strate that αβ chain pairs are significantly more informative than individual chains alone. These findings provide unprecedented insight into the CD4 + and CD8 + TCR repertoires and highlight the importance of αβ chain pairing in TCR function and specificity.