Department of Radiation Oncology, Physiology and Biophysics, Englander Institute of Precision Medicine, Weill Cornell Medicine, New York, NY, United States.
University of California San Diego School of Medicine, Department of Pediatrics, La Jolla, CA, United States.
Front Immunol. 2022 Nov 2;13:1035363. doi: 10.3389/fimmu.2022.1035363. eCollection 2022.
The MHC- immunopeptidome of professional antigen presenting cells is a cognate ligand for the TCRs expressed on both conventional and thymic-derived natural regulatory T cells. In regulatory T cells, the TCR signaling associated with MHC-peptide recognition induces antigen specific as well as bystander immunosuppression. On the other hand, TCR activation of conventional T cells is associated with protective immunity. As such the peripheral T cell repertoire is populated by a number of T cells with different phenotypes and different TCRs, which can recognize the same MHC-self-peptide complex, resulting in opposite immunological outcomes. This article summarizes what is known about regulatory and conventional T cell recognition of the MHC-self-immunopeptidome at steady state and in inflammatory conditions associated with increased T and B cell self-reactivity, discussing how changes in the MHC-ligandome including epitope copy number and post-translational modifications can tilt the balance toward the expansion of pro-inflammatory or regulatory T cells.
主要组织相容性复合体（MHC）-免疫肽组是表达于常规和胸腺来源的天然调节性 T 细胞（nTreg）TCR 的同源配体。在调节性 T 细胞中，与 MHC-肽识别相关的 TCR 信号转导诱导抗原特异性和旁观者免疫抑制。另一方面，常规 T 细胞的 TCR 激活与保护性免疫相关。因此，外周 T 细胞库中存在许多具有不同表型和不同 TCR 的 T 细胞，这些 TCR 可以识别相同的 MHC-自身肽复合物，从而产生相反的免疫学结果。本文总结了在稳态和与 T、B 细胞自身反应性增加相关的炎症条件下，调节性和常规 T 细胞对 MHC-自身免疫肽组的识别，讨论了 MHC 配体组（包括表位拷贝数和翻译后修饰）的变化如何使炎症性或调节性 T 细胞的扩增失衡。
