Diversity and clonal selection in the human T-cell repertoire

• DOI: 10.1073/pnas.1409155111
• Publication Date: 2014-08-26T03:20:35Z
• Authors: Qian Qi; Yi Liu; Yong Cheng; Jacob Glanville; David Zhang; Ji-Yeun Lee; Richard A. Olshen; Cornelia M. Weyand; Scott D. Boyd; Jörg J. Goronzy
• Keywords: Adult; CD4-Positive T-Lymphocytes; Aging; Base Sequence; T-Lymphocytes; Receptors, Antigen, T-Cell; CD8-Positive T-Lymphocytes; Complementarity Determining Regions; Cell Compartmentation; Clone Cells; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Cytokines; Humans; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Immunologic Memory; Aged; Cell Proliferation

T-cell receptor (TCR) diversity, a prerequisite for immune system recognition of the universe foreign antigens, is generated in first two decades life thymus and then persists to an unknown extent through via homeostatic proliferation naïve T cells. We have used next-generation sequencing nonparametric statistical analysis estimate lower bound total number different TCR beta (TCRB) sequences human repertoires. arrived at surprisingly high minimal estimates 100 million unique TCRB CD4 CD8 repertoires young adults. Naïve repertoire richness modestly declined two- fivefold healthy elderly. Repertoire contraction with age was even less pronounced memory In contrast, had major impact on inequality clonal sizes, as estimated by modified Gini-Simpson index clonality score. particular, large clones that were distinct from found elderly individuals, indicating uneven without development cell phenotype. Our results suggest highly diverse maintained despite thymic involution; however, peripheral fitness selection cells leads perturbations can influence response