Human T-cell memory consists mainly of unexpanded clones

Immunology Letters
Paul L KlarenbeekN de Vries

Abstract

The immune system is able to respond to millions of antigens using adaptive receptors, including the alphabeta-T-cell receptor (TCR). Upon antigen encounter a T-cell may proliferate to produce a clone of TCR-identical cells, which develop a memory phenotype. Previous studies suggested that most memory clones are clearly expanded. In accordance, the beta-chain repertoire of T-cell memory subsets was reported to be 10 times less diverse than those of naive subsets, reflecting stringent selection. However, due to technological limitations detailed information was lacking regarding the size of clonal expansions and the diversity of the TCR-repertoire in naive and memory T-cell populations. Here, using high-throughput sequencing, we show that the memory repertoire in human peripheral blood contains only few expanded clones and consists mainly of low frequency clones. Additionally, the memory repertoire is much more diverse than expected. In two healthy persons we observed that only 2-7% of the CD4 and CD8 memory clones found were clearly expanded. In line with this observation we show that the beta-chains repertoire size of the CD4 memory compartment is only two times smaller, and that of the CD8 memory compartment is only 3-10 time...Continue Reading

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