Objective: To investigate whether stimulation with toll-like receptor (TLR) 7 leads to pathways that proceed to tripartite motif-containing protein 21 (TRIM21) or Ro52/SS-A antigen presentation through major histocompatibility complex (MHC) class I in salivary gland epithelial cells (SGECs) from Sjögren’s syndrome (SS) patients. Design and Methods: Cultured SGECs from SS patients were stimulated with TLR7 agonist, loxoribine, and interferon-β. Cell lysates immunoprecipitated by anti-MHC class I antibody were analyzed by Western blotting. The immunofluorescence of salivary gland tissue from SS and non-SS subjects and cultured TLR7-stimulated SGECs was examined. Results: Significantly increased MHC class I expression was observed in SS patients’ ducts versus non-SS ducts; no significant difference was detected for ubiquitin. Upregulated MHC class I in the cell membrane and cytoplasm and augmented Ro52 expression were observed in SGECs stimulated with TLR7. The formation of peptide-loading complex (PLC), including tapasin, calreticulin, transporter associated with antigen processing 1, and endoplasmic reticulum-resident protein 57 in labial salivary glands (LSGs) from SS patients, was dominantly observed and colocalized with MHC class I, which was confirmed in TLR7-stimulated SGEC samples. Conclusion: These findings suggest that the TLR7 stimulation of SS patients’ SGECs advances the process toward the antigen presentation of TRIM21/Ro52-SS-A via MHC class I.