Generation of self-reactive, shared T-cell receptor α chains in the human thymus
Loading...
Access rights
openAccess
URL
Journal Title
Journal ISSN
Volume Title
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
This publication is imported from Aalto University research portal.
View publication in the Research portal (opens in new window)
View/Open full text file from the Research portal (opens in new window)
Other link related to publication (opens in new window)
View publication in the Research portal (opens in new window)
View/Open full text file from the Research portal (opens in new window)
Other link related to publication (opens in new window)
Date
2021-05
Department
Major/Subject
Mcode
Degree programme
Language
en
Pages
Series
JOURNAL OF AUTOIMMUNITY, Volume 119
Abstract
The T-cell receptor (TCR) repertoire is generated in a semistochastic process of gene recombination and pairing of TCRα to TCRβ chains with the estimated total TCR diversity of >108. Despite this high diversity, similar or identical TCR chains are found to recur in immune responses. Here, we analyzed the thymic generation of TCR sequences previously associated with recognition of self- and nonself-antigens, represented by sequences associated with autoimmune diabetes and HIV, respectively. Unexpectedly, in the CD4+ compartment TCRα chains associated with the recognition of self-antigens were generated in significantly higher numbers than TCRα chains associated with the recognition of nonself-antigens. The analysis of the circulating repertoire further showed that these chains are not lost in negative selection nor predominantly converted to the regulatory T-cell lineage. The high abundance of self-reactive TCRα chains in multiple individuals suggests that the human thymus has a predilection to generate self-reactive TCRα chains independently of the HLA-type and that the individual risk of autoimmunity may be modulated by the TCRβ repertoire associated with these chains.Description
Keywords
Autoantigen, Autoimmunity, T cell receptor, T cell recombination, Thymic selections, Thymus
Other note
Citation
Heikkilä, N, Sormunen, S, Mattila, J, Härkönen, T, Knip, M, Ihantola, E L, Kinnunen, T, Mattila, I P, Saramäki, J & Arstila, T P 2021, ' Generation of self-reactive, shared T-cell receptor α chains in the human thymus ', Journal of Autoimmunity, vol. 119, 102616 . https://doi.org/10.1016/j.jaut.2021.102616