MHC-Unrestricted Lysis of MUC1-Expressing Cells by Human Peripheral Blood Mononuclear Cells

• Published in: Immunological investigations 2008-01, Vol.37 (3), p.215-225
• Main Authors: Wright, Stephen E., Rewers-Felkins, Kathleen A., Quinlin, Imelda S., Fogler, William E., Phillips, Catherine A., Townsend, Mary, Robinson, William, Philip, Ramila
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma - metabolism; Animals; Antibodies, Neoplasm - immunology; Antibodies, Neoplasm - metabolism; Antigen-Presenting Cells - immunology; Antigens, Neoplasm - biosynthesis; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; CD4-Positive T-Lymphocytes - immunology; Cell death; Cytotoxicity, Immunologic; Epitopes; Female; Humans; Immunodominant Epitopes - immunology; Leukocytes, Mononuclear - immunology; Lymphocyte Activation; Major histocompatibility complex; Major Histocompatibility Complex - immunology; Mammary Neoplasms, Animal - immunology; Mammary Neoplasms, Animal - metabolism; Mice; Mucin-1 - chemistry; Mucin-1 - immunology; Mucins human; Transgenes; Tumor Cells, Cultured
• ISSN: 0882-0139; 1532-4311
• DOI: 10.1080/08820130801967874

Many human adenocarcinomas can be killed in vitro by targeted cytotoxic T-lymphocytes (CTL); however, major histocompatibility complex (MHC)-restrictions are typically required. The MUC1 antigen is common in many human adenocarcinomas, and is associated with a variable number of tandem repeats. It has been proposed that antigens with such repeated epitopes may be vulnerable to cytotoxic T-lymphocyte killing without MHC-restriction. Therefore, it is possible that MUC1-expressing malignant cells may be killed by targeted cytotoxic T-lymphocyte in the absence of MHC-restriction. In this study, a human MUC1-expressing murine mammary carcinoma cell line was used to determine if cytotoxic T-lymphocyte killing of MUC1-expressing adenocarcinoma cells requires MHC-restriction. Specifically, MUC1-stimulated human mononuclear cells (M1SMC) were observed to kill human MUC1-transfected, MUC1-expressing murine mammary carcinoma cells, but not the mock-transfected, non-MUC1-expressing murine mammary carcinoma cells. Furthermore, the killing was blocked by antibody to MUC1, indicating MUC1-specific killing. In conclusion, cytotoxic T-lymphocyte killing of MUC1-expressing adenocarcinoma cells can be MHC-unrestricted.