Characteristics of T-cell receptor repertoire of stem cell-like memory CD4+ T cells

Abstract

Stem cell-like memory T cells (Tscm) combine phenotypes of naïve and memory. However, it remains unclear how T cell receptor (TCR) characteristics contribute to heterogeneity in Tscm and other memory T cells. We compared the TCR-beta (TRB) repertoire characteristics of CD4+ Tscm with those of naïve and other CD4+ memory (Tm) in 16 human subjects. Compared with Tm, Tscm had an increased diversity across all stretches of TRB repertoire structure, a skewed gene usage, and a shorter length distribution of CDR3 region. These distinctions between Tscm and Tm were enlarged in top1000 abundant clonotypes. Furthermore, top1000 clonotypes in Tscm were more public than those in Tm and grouped in more clusters, implying more epitope types recognized by top1000 clonotypes in Tscm. Importantly, self-reactive clonotypes were public and enriched in Tscm rather than Tm, of type one diabetes patients. Therefore, this study highlights the unique features of Tscm different from those of other memory subsets and provides clues to understand the physiological and pathological functions of Tscm.