Publication details

Dynamics of Individual T Cell Repertoires: From Cord Blood to Centenarians

Authors	BRITANOVA Olga SHUGAY Mikhail MERZLYAK Ekaterina M. STAROVEROV Dmitriy B. PUTINTSEVA Ekaterina V. TURCHANINOVA Maria A. MAMEDOV Ilgar POGORELYY Mikhail V. BOLOTIN Dmitry IZRAELSON Mark DAVYDOV Alexey Nikolayevich EGOROV Evgeny KASATSKAYA Sofya A. REBRIKOV Denis V. LUKYANOV Sergey CHUDAKOV Dmitriy
Year of publication	2016
Type	Article in Periodical
Magazine / Source	Journal of immunology
MU Faculty or unit	Central European Institute of Technology
Citation
Web	http://www.jimmunol.org/content/196/12/5005
Doi	http://dx.doi.org/10.4049/jimmunol.1600005
Field	Epidemiology, infectious diseases and clinical immunology
Keywords	UNIQUE MOLECULAR IDENTIFIERS; MEDIATED RNA DECAY; RECEPTOR REPERTOIRES; HUMAN CYTOMEGALOVIRUS; CLONAL EXPANSIONS; GENE-EXPRESSION; IMMUNE REPERTOIRES; ANTIGEN RECEPTORS; NONSENSE CODONS; TCR DIVERSITY
Description	The diversity, architecture, and dynamics of the TCR repertoire largely determine our ability to effectively withstand infections and malignancies with minimal mistargeting of immune responses. In this study, we have employed deep TCRb repertoire sequencing with normalization based on unique molecular identifiers to explore the long-term dynamics of T cell immunity. We demonstrate remarkable stability of repertoire, where approximately half of all T cells in peripheral blood are represented by clones that persist and generally preserve their frequencies for 3 y. We further characterize the extremes of lifelong TCR repertoire evolution, analyzing samples ranging from umbilical cord blood to centenarian peripheral blood. We show that the fetal TCR repertoire, albeit structurally maintained within regulated borders due to the lower numbers of randomly added nucleotides, is not limited with respect to observed functional diversity. We reveal decreased efficiency of nonsense-mediated mRNA decay in umbilical cord blood, which may reflect specific regulatory mechanisms in development. Furthermore, we demonstrate that human TCR repertoires are functionally more similar at birth but diverge during life, and we track the lifelong behavior of CMV- and EBVspecific T cell clonotypes. Finally, we reveal gender differences in dynamics of TCR diversity constriction, which come to naught in the oldest age. Based on our data, we propose a more general explanation for the previous observations on the relationships between longevity and immunity.