T cells recognize and respond to self antigens in both cancer and autoimmunity. One strategy to influence this response is to incorporate amino acid substitutions into these T cell-specific epitopes. This strategy is being reconsidered now with the goal of increasing time to regression with checkpoint blockade therapies in cancer and antigen-specific immunotherapies in autoimmunity. We discuss how these amino acid substitutions change the interactions with the MHC class I or II molecule and the responding T cell repertoire. Amino acid substitutions in epitopes that are the most effective in therapies bind more strongly to T cell receptor and/or MHC molecules and cross-react with the same repertoire of T cells as the natural antigen.

T细胞在癌症和自身免疫中均能识别自身抗原并对其作出反应。影响该反应的一种策略是将氨基酸取代并入这些T细胞特异性表位。现在正在重新考虑此策略，目的是增加癌症检查点封锁疗法和自身免疫的抗原特异性免疫疗法的消退时间。我们讨论了这些氨基酸取代如何改变与MHC I类或II类分子和响应性T细胞库的相互作用。在治疗中最有效的表位中的氨基酸取代与T细胞受体和/或MHC分子的结合更牢固，并与天然抗原具有相同的T细胞库交叉反应。