人类主要组织相容性复合体 (MHC) 在蛋白质肽片段的呈递中发挥着关键作用，这些肽片段可以源自自身蛋白质或非人类抗原，例如由病毒或细菌产生的抗原。为了防止对健康细胞的细胞毒性，表达识别自肽的 T 细胞受体 (TCR) 的胸腺细胞被从循环中去除（阴性选择），从而留下识别非自肽的 T 细胞。目前的理解表明，翻译后修饰（PTM）蛋白及其在蛋白水解后产生的肽片段在很大程度上被排除在负选择之外；这一特征意味着 PTM 可以产生非自身肽，可能有助于自身反应性 T 细胞和随后的自身免疫性疾病的发展。尽管众所周知 PTM 在 MHC 上存在的肽中普遍存在，但 PTM 影响抗原呈递机制的精确机制仍然知之甚少。在目前的工作中，我们引入了模拟合成肽 PTM 的化学修饰。这是第一个系统研究分离 PTM 对 MHC 结合的影响以及它们对 TCR 识别的影响。我们的研究结果揭示了 PTM 改变抗原呈递的多种方式，这可能对肿瘤新抗原呈递产生影响。

The human major histocompatibility complex (MHC) plays a pivotal role in the presentation of peptidic fragments from proteins, which can originate from self-proteins or from nonhuman antigens, such as those produced by viruses or bacteria. To prevent cytotoxicity against healthy cells, thymocytes expressing T cell receptors (TCRs) that recognize self-peptides are removed from circulation (negative selection), thus leaving T cells that recognize nonself-peptides. Current understanding suggests that post-translationally modified (PTM) proteins and the resulting peptide fragments they generate following proteolysis are largely excluded from negative selection; this feature means that PTMs can generate nonself-peptides that potentially contribute to the development of autoreactive T cells and subsequent autoimmune diseases. Although it is well-established that PTMs are prevalent in peptides present on MHCs, the precise mechanisms by which PTMs influence the antigen presentation machinery remain poorly understood. In the present work, we introduce chemical modifications mimicking PTMs on synthetic peptides. This is the first systematic study isolating the impact of PTMs on MHC binding and also their impact on TCR recognition. Our findings reveal various ways PTMs alter antigen presentation, which could have implications for tumor neoantigen presentation.