Department of Immunology and Microbiology, University of Colorado School of Medicine, 12800 E. 19thAvenue, Aurora, CO 80045, USA.
Department of Immunology and Microbiology, University of Colorado School of Medicine, 12800 E. 19thAvenue, Aurora, CO 80045, USA; Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, 1775 Aurora Court, Aurora, CO 80045, USA.
Semin Immunol. 2020 Feb;47:101395. doi: 10.1016/j.smim.2020.101395. Epub 2020 Mar 20.
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识别和响应自身抗原。影响这种反应的一种策略是在这些 T 细胞特异性表位中引入氨基酸取代。现在，人们重新考虑了这一策略，目的是在癌症的检查点阻断疗法和自身免疫的抗原特异性免疫疗法中，增加消退时间。我们讨论了这些氨基酸取代如何改变与 MHC Ⅰ类或Ⅱ类分子以及反应性 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 分子结合更牢固，并且与天然抗原的相同 T 细胞库发生交叉反应。
