This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
Cite this article
Usharauli D, Kamala T.2019. Shared TCR epitope cross-reactivity could permit dyads of Foxp3+ regulatory and IL-2-producing T cell precursors to escape thymic purge. PeerJ Preprints7:e27853v1https://doi.org/10.7287/peerj.preprints.27853v1
The thymus-derived Foxp3+ regulatory T cells (Tregs) represent a unique population of CD4+ T cells responsible for maintaining dominant tolerance to auto-antigens, beneficial microbiota and potential irritants such as allergens on the one hand and efficient but balanced defense against pathogens on the other. How Tregs with high-affinity TCRs for thymically expressed epitopes survive thymic deletion or display such broad functionality is presently unclear. We recently introduced a novel framework dubbed SPIRAL (SPecific ImmunoRegulatory ALgorithm) which suggests that antigen cross-reactivity of thymic Treg repertoire could provide a mechanistic basis for its broad functionality. Here we further develop this model to propose how escape of high-affinity Tregs from thymic purge could be achieved in dyads with high-affinity natural IL-2-producing T cells (IL-2p T cells) sharing TCR epitope cross-reactivity. We believe this interpretation could reconcile contradictions related to Treg ontogeny in the thymus and their role in modulating antigen-specific immune responses.