Chiriţoiu Gabriela N, Munteanu Cristian V A, Şulea Teodor A, Spiridon Laurenţiu, Petrescu Andrei-Jose, Jandus Camilla, Romero Pedro, Petrescu Ştefana M
Department of Molecular Cell Biology, Institute of Biochemistry, Splaiul Independenței 296, 060031 Bucharest, Romania.
Department of Bioinformatics and Structural Biochemistry, Institute of Biochemistry, Splaiul Independenței 296, 060031 Bucharest, Romania.
iScience. 2023 Jun 25;26(7):107205. doi: 10.1016/j.isci.2023.107205. eCollection 2023 Jul 21.
The impact of the peptide amino acids side-chain modifications on the immunological recognition has been scarcely explored. We investigate here the effect of methionine oxidation on the antigenicity of the melanoma immunodominant peptide 369-YMDGTMSQV-377 (YMD). Using CD8 T cell activation assays, we found that the antigenicity of the sulfoxide form is higher when compared to the YMD peptide. This is consistent with free energy computations performed on HLA-A∗02:01/YMD/TCR complex showing that this is lowered upon oxidation, paired with a steep increase in order at atomic level. Oxidized YMD forms were identified at the melanoma cell surface by LC-MS/MS analysis. These results demonstrate that methionine oxidation in the antigenic peptides may generate altered peptide ligands with increased antigenicity, and that this oxidation may occur , opening up the possibility that high-affinity CD8 T cells might be naturally primed in the course of melanoma progression, as a result of immunosurveillance.
肽氨基酸侧链修饰对免疫识别的影响鲜有研究。我们在此研究甲硫氨酸氧化对黑色素瘤免疫优势肽369 - YMDGTMSQV - 377（YMD）抗原性的影响。通过CD8 T细胞活化试验，我们发现与YMD肽相比，亚砜形式的抗原性更高。这与对HLA - A∗02:01/YMD/TCR复合物进行的自由能计算结果一致，该计算表明氧化后其自由能降低，同时原子水平的有序度急剧增加。通过LC - MS/MS分析在黑色素瘤细胞表面鉴定出了氧化的YMD形式。这些结果表明，抗原肽中的甲硫氨酸氧化可能产生抗原性增加的改变肽配体，并且这种氧化可能会发生，这就开启了一种可能性，即作为免疫监视的结果，在黑色素瘤进展过程中可能会天然引发高亲和力CD8 T细胞。
