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

• DOI: 10.1016/j.jaut.2021.102616
• Publication Date: 2021-02-27T13:45:24Z
• Authors: Nelli Heikkilä; Silja Sormunen; Joonatan Mattila; Taina Härkönen; Mikael Knip; Emmi-Leena Ihantola; Tuure Kinnunen; Ilkka P. Mattila; Jari Saramäki; T. Petteri Arstila
• Keywords: Negative selection

The T-cell receptor (TCR) repertoire is generated in a semistochastic process of gene recombination and pairing TCRα to TCRβ chains with the estimated total TCR diversity >108. Despite this high diversity, similar or identical are found recur immune responses. Here, we analyzed thymic generation sequences previously associated recognition self- nonself-antigens, represented by autoimmune diabetes HIV, respectively. Unexpectedly, CD4+ compartment self-antigens were significantly higher numbers than nonself-antigens. analysis circulating further showed that these not lost negative selection nor predominantly converted regulatory lineage. abundance self-reactive multiple individuals suggests human thymus has predilection generate independently HLA-type individual risk autoimmunity may be modulated chains.