Generation of self-reactive, shared T-cell receptor ? chains in the human thymus

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Heikkilä , N , Sormunen , S , Mattila , J , Härkönen , T , Knip , M , Ihantola , E-L , Kinnunen , T , Mattila , I P , Sarama , J & Arstila , T P 2021 , ' Generation of self-reactive, shared T-cell receptor ? chains in the human thymus ' , Journal of Autoimmunity , vol. 119 , 102616 . https://doi.org/10.1016/j.jaut.2021.102616

Title: Generation of self-reactive, shared T-cell receptor ? chains in the human thymus
Author: Heikkilä, Nelli; Sormunen, Silja; Mattila, Joonatan; Härkönen, Taina; Knip, Mikael; Ihantola, Emmi-Leena; Kinnunen, Tuure; Mattila, Ilkka P.; Sarama, Jari; Arstila, T. Petteri
Contributor organization: TRIMM - Translational Immunology Research Program
Medicum
Research Programs Unit
University of Helsinki
Department of Bacteriology and Immunology
Staff Services
HUS Children and Adolescents
Children's Hospital
Lastentautien yksikkö
CAMM - Research Program for Clinical and Molecular Metabolism
Petteri Arstila / Principal Investigator
Date: 2021-05
Language: eng
Number of pages: 9
Belongs to series: Journal of Autoimmunity
ISSN: 0896-8411
DOI: https://doi.org/10.1016/j.jaut.2021.102616
URI: http://hdl.handle.net/10138/330936
Abstract: The T-cell receptor (TCR) repertoire is generated in a semistochastic process of gene recombination and pairing of TCR? to TCR? 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 TCR? chains associated with the recognition of self-antigens were generated in significantly higher numbers than TCR? 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 TCR? chains in multiple individuals suggests that the human thymus has a predilection to generate self-reactive TCR? chains independently of the HLA-type and that the individual risk of autoimmunity may be modulated by the TCR? repertoire associated with these chains.
Subject: T cell receptor
T cell recombination
Thymus
Thymic selections
Autoantigen
Autoimmunity
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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