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Human T-cell memory consists mainly of unexpanded clones
Klarenbeek, Paul L.1; Tak, Paul P.1; van Schaik, Barbera D. C.2; Zwinderman, Aeilko H.2; Jakobs, Marja E.3; Zhang, Zhuoli5; van Kampen, Antoine H. C.2,6; van Lier, Rene A. W.4; Baas, Frank3; de Vries, Niek1
关键词T-cell Receptor Repertoire Clonal Make-up Of Naive And Memory T-cell Subsets Humans High-throughput Sequencing Diversity Estimates
WOS标题词Science & Technology

The immune system is able to respond to millions of antigens using adaptive receptors, including the alpha beta-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 times smaller than the naive compartments. Our results show that the T-cell memory compartment has a very different distribution of clones than anticipated. This has important implications for the current dogma of immunological memory, and changes the interpretation of repertoire aberrations in (patho-)physiological situations such as ageing and auto-immunity. It raises new questions on the factors that steer maturation of memory phenotype and determine the size of memory clones. (C) 2010 Elsevier B.V. All rights reserved.

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作者单位1.Univ Amsterdam, AMC, Dept Clin Immunol & Rheumatol, NL-1012 WX Amsterdam, Netherlands
2.Univ Amsterdam, AMC, Dept Clin Epidemiol Biostat & Bioinformat, NL-1012 WX Amsterdam, Netherlands
3.Univ Amsterdam, AMC, Dept Genome Anal, NL-1012 WX Amsterdam, Netherlands
4.Univ Amsterdam, AMC, Dept Expt Immunol, NL-1012 WX Amsterdam, Netherlands
5.Beijing Univ, Hosp 1, Dept Rheumatol & Clin Immunol, Beijing 100871, Peoples R China
6.Univ Amsterdam, Swammerdam Inst Life Sci, NL-1012 WX Amsterdam, Netherlands
Recommended Citation
GB/T 7714
Klarenbeek, Paul L.,Tak, Paul P.,van Schaik, Barbera D. C.,et al. Human T-cell memory consists mainly of unexpanded clones[J]. IMMUNOLOGY LETTERS,2010,133(1):42-48.
APA Klarenbeek, Paul L..,Tak, Paul P..,van Schaik, Barbera D. C..,Zwinderman, Aeilko H..,Jakobs, Marja E..,...&de Vries, Niek.(2010).Human T-cell memory consists mainly of unexpanded clones.IMMUNOLOGY LETTERS,133(1),42-48.
MLA Klarenbeek, Paul L.,et al."Human T-cell memory consists mainly of unexpanded clones".IMMUNOLOGY LETTERS 133.1(2010):42-48.
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