Tregeutix Inc., Orlando, FL, USA.
Scand J Immunol. 2021 Jan;93(1):e12940. doi: 10.1111/sji.12940. Epub 2020 Aug 10.
Thymocytes that bind with high affinity to peptides displayed by MHC class II (pMHC-II) are deleted while low-affinity binders differentiate into naive CD4+ T cells. However, Foxp3+ regulatory T cells (Tregs) seem to defy this binary choice as their precursors require high-affinity interaction with pMHC-II for maturation in the thymus. Here, we rely on the antigen-specific interpretive framework, SPIRAL (Specific ImmunoRegulatory Algorithm), to propose that Tregs escape thymic deletion by forming dyads with IL-2-producing T cells via antigen cross-reactivity. This interpretation reconciles contradictions related to Treg ontogeny in the thymus and their role in modulating antigen-specific immune responses.
高亲和力结合 MHC Ⅱ类（pMHC-II）所展示肽段的胸腺细胞被删除，而低亲和力结合物则分化为幼稚 CD4+T 细胞。然而，Foxp3+调节性 T 细胞（Tregs）似乎违背了这种二元选择，因为它们的前体需要与 pMHC-II 高亲和力相互作用才能在胸腺中成熟。在这里，我们依赖于抗原特异性解释框架 SPIRAL（Specific ImmunoRegulatory Algorithm），提出 Tregs 通过抗原交叉反应与产生 IL-2 的 T 细胞形成二聚体，从而逃避胸腺删除。这种解释调和了与胸腺中 Treg 发生和它们在调节抗原特异性免疫反应中的作用相关的矛盾。
