Key Points Posttranslationally methylated peptides can be recognized by human T cells. Methyl lysines are part of the T cell epitope on heparin-binding hemagglutinin. Methylated peptides induce IFN-γ secretion upon M. tuberculosis infection. T cell epitopes are mostly nonmodified peptides, although posttranslationally modified peptide epitopes have been described, but they originated from viral or self-proteins. In this study, we provide evidence of a bacterial methylated T cell peptide epitope. The mycobacterial heparin-binding hemagglutinin (HBHA) is a protein Ag with a complex C-terminal methylation pattern and is recognized by T cells from humans latently infected with Mycobacterium tuberculosis. By comparing native HBHA with recombinant HBHA produced in Mycobacterium smegmatis (rHBHA-Ms), we could link antigenic differences to differences in the methylation profile. Peptide scan analyses led to the discovery of a peptide containing methyl lysines recognized by a mAb that binds to native HBHA ∼100-fold better than to rHBHA-Ms. This peptide was also recognized by T cells from latently infected humans, as evidenced by IFN-γ release upon peptide stimulation. The nonmethylated peptide did not induce IFN-γ, arguing that the methyl lysines are part of the T cell epitope.

中文翻译：

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分枝杆菌肝素结合血凝素上含有甲基赖氨酸的天然 T 细胞表位

关键点翻译后甲基化肽可以被人类 T 细胞识别。甲基赖氨酸是肝素结合血凝素 T 细胞表位的一部分。甲基化肽在结核分枝杆菌感染后诱导 IFN-γ 分泌。T细胞表位大多是未修饰的肽，虽然已经描述了翻译后修饰的肽表位，但它们起源于病毒或自身蛋白。在这项研究中，我们提供了细菌甲基化 T 细胞肽表位的证据。分枝杆菌肝素结合血凝素 (HBHA) 是一种蛋白质 Ag，具有复杂的 C 端甲基化模式，可被潜伏感染结核分枝杆菌的人类 T 细胞识别。通过比较天然 HBHA 与耻垢分枝杆菌 (rHBHA-Ms) 中产生的重组 HBHA，我们可以将抗原差异与甲基化谱的差异联系起来。肽扫描分析导致发现了一种含有甲基赖氨酸的肽，该肽被 mAb 识别，与天然 HBHA 的结合比与 rHBHA-Ms 的结合好约 100 倍。这种肽也被来自潜伏感染人类的​​ T 细胞识别，正如肽刺激后 IFN-γ 的释放所证明的那样。非甲基化肽不诱导 IFN-γ，认为甲基赖氨酸是 T 细胞表位的一部分。