Mass spectrometry (MS)-based immunopeptidomics has developed as one of the leading methodologies for comprehensive characterization of in vivo presented human leukocyte antigen (HLA)-bound peptides. Unveiling the identity of HLA-bound peptides derived from diseased cells is crucial to gain knowledge on the constitution of efficient disease-specific T cell responses. The HLA-presented peptidome reflects the status of the cellular proteome, hence disease-related aberrations of posttranslational modifications (PTMs) might lead to presentation of peptides harboring PTMs. Therefore, characterization of HLA-bound PTM peptides could shed light on their relevance in immune and disease processes. In this issue, Ramarathinam et al. investigate the presentation of HIV envelope (HIVenv) peptides bound to the HLA-B*57:01 allele. Among these peptides, the authors specifically focused on a kynurenine-modified peptide. To this end, they characterize the possible origin of the kynurenine modification, its effect on HLA binding affinity, stability, conformation within the complex, and its immunogenicity compared to the native counterpart.