Methionine oxidation selectively enhances T cell reactivity against a melanoma antigen

Gabriela N Chiriţoiu; Cristian V A Munteanu; Teodor A Şulea; Laurenţiu Spiridon; Andrei-Jose Petrescu; Camilla Jandus; Pedro Romero; Ştefana M Petrescu

doi:10.1016/j.isci.2023.107205

Methionine oxidation selectively enhances T cell reactivity against a melanoma antigen

iScience. 2023 Jun 25;26(7):107205. doi: 10.1016/j.isci.2023.107205. eCollection 2023 Jul 21.

Authors

Gabriela N Chiriţoiu¹, Cristian V A Munteanu², Teodor A Şulea², Laurenţiu Spiridon², Andrei-Jose Petrescu², Camilla Jandus^{3

4}, Pedro Romero⁵, Ştefana M Petrescu¹

Affiliations

¹ Department of Molecular Cell Biology, Institute of Biochemistry, Splaiul Independenței 296, 060031 Bucharest, Romania.
² Department of Bioinformatics and Structural Biochemistry, Institute of Biochemistry, Splaiul Independenței 296, 060031 Bucharest, Romania.
³ Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
⁴ Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
⁵ Departement of Oncology, UNIL-CHUV, University of Lausanne, Epalinges, Switzerland.

Abstract

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 in vivo, 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.

Keywords: Biochemistry; Cancer; Immunology.