Immunopeptidomic profiling identifies lesion associated peptides in oral lichen planus

Although cytotoxic T cells are thought to play a central role in oral lichen planus (OLP) pathogenesis, the peptides potentially involved in these immune responses remain largely unknown. Characterizing peptides presented by major histocompatibility complex (MHC) molecules in diseased tissues may provide insights into antigen presentation in OLP. We performed immunopeptidomic profiling of paired OLP lesions and clinically normal appearing adjacent mucosal tissues from three patients. Comparative analyses were conducted to identify peptides preferentially detected or enriched in OLP lesions. A representative HLA class I-associated peptide was chemically synthesized and subsequently evaluated in vivo using systemic peptide immunization followed by local oral peptide rechallenge. A total of 44,839 unique HLA class I-associated peptides and 48,719 unique HLA class II-associated peptides were identified across the OLP samples. Comparative analysis identified lesion associated peptide repertoires, including 421 HLA class I-associated peptides and 188 HLA class II-associated peptides detected across all three OLP lesions. Additional shared peptides showed increased abundance in OLP lesions. In vivo evaluation of a representative HLA class I-associated peptide showed that local peptide rechallenge following prior systemic immunization was associated with inflammatory histological changes and changes in T cell populations in oral tissues. These findings provide an initial characterization of the MHC associated peptide landscape in OLP and identify candidate peptides for further investigation of antigen presentation and peptide associated immune responses in this disease. The naturally presented peptide repertoire in OLP remains poorly characterized despite the important role of T cells in disease pathogenesis. This study provides an initial immunopeptidomic characterization of OLP lesions and paired adjacent mucosa and identifies candidate peptides that may facilitate future studies of antigen presentation and T cell immune responses in OLP. We performed immunopeptidomic profiling of paired OLP lesions and adjacent mucosa, providing an initial characterization of the MHC-associated peptide landscape in OLP. Comparative analysis identified peptides preferentially detected or enriched in OLP lesions. A representative HLA class I-associated peptide was further evaluated in vivo using systemic peptide immunization followed by local oral peptide rechallenge, which was associated with increased leukocyte infiltration and T cell population changes. These findings provide candidate peptides for further investigation of antigen presentation and peptide-associated immune responses in OLP.