Paper - Review

DOI: 10.1073/pnas.1409155111

Abstract

T-cell receptor (TCR) diversity
← a prerequisite → for (immune system recognition) ← of the universe of foreign antigens
→ is generated ← in the first two decades of life ← in the thymus
→ persist → to an unknown extent
← through life ← via homeostatic proliferation of naïve T cells

❗: Used → 1⃣ next-generation sequencing 2⃣ non-parametric statistical analysis
→ to estimate a lower bound → for the total number of different TCR beta (TCRB) sequences
← in human repertoires

❗: Arrived → at surprisingly high minimal estimates of 100 million unique TCRB sequences
← in naïve 1⃣ CD4 2⃣ CD8 T-cell repertoires ← of young adults

Naïve repertoire richness
→ declined 2- to 5-fold ← in healthy elderly

❗: repertoire richness
← contraction with age
→ was even less pronounced → for 1⃣ memory CD4 2⃣ CD8 T-cells

❗: Age → had a major impact
← on the inequality of (clonal sizes)
← as estimated by a modified Gini-Simpson index clonality score

❗: large naïve T-cell clones
← that were distinct ← from memory clones
→ were found ← in the repertoires of (elderly individuals)
∴ Uneven homeostatic proliferation
← without development ← of a memory cell phenotype

∴ A highly diverse repertoire → is maintained
← despite thymic involution
∴ Peripheral fitness selection of T-cells
→ leads to repertoire perturbations
← that can influence (the immune response) ← in the elderly

---