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However, Foxp3+ regulatory T cells (Tregs) seem to defy this binary choice as their precursors require high\u2010affinity interaction with pMHC\u2010II for maturation in the thymus. Here, we rely on the antigen\u2010specific interpretive framework, SPIRAL (<jats:styled-content>Sp<\/jats:styled-content>ecific <jats:styled-content>I<\/jats:styled-content>mmuno<jats:styled-content>R<\/jats:styled-content>egulatory <jats:styled-content>Al<\/jats:styled-content>gorithm), to propose that Tregs escape thymic deletion by forming dyads with IL\u20102\u2010producing T cells via antigen cross\u2010reactivity. This interpretation reconciles contradictions related to Treg ontogeny in the thymus and their role in modulating antigen\u2010specific immune responses.<\/jats:p>","DOI":"10.1111\/sji.12940","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T20:20:12Z","timestamp":1595449212000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Could cross\u2010reactivity rescue Foxp3+ regulatory T cell precursors from thymic deletion?"],"prefix":"10.1111","volume":"93","author":[{"given":"David","family":"Usharauli","sequence":"first","affiliation":[{"name":"Tregeutix Inc. Orlando FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6340-8597","authenticated-orcid":false,"given":"Tirumalai","family":"Kamala","sequence":"additional","affiliation":[{"name":"Tregeutix Inc. 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