MHC-unrestricted lysis of MUC1-expressing cells by human peripheral blood mononuclear cells.
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.
Wright
Stephen E
SE
Amarillo Veterans Affairs Health Care System, Amarillo, Texas 79106, USA. stephen.wright@med.va.gov
Rewers-Felkins
Kathleen A
KA
Quinlin
Imelda S
IS
Fogler
William E
WE
Phillips
Catherine A
CA
Townsend
Mary
M
Robinson
William
W
Philip
Ramila
R
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology*; D015674:Mammary Neoplasms, Animal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018396:Mucin-1 / Q000737:chemistry / Q000276:immunology*; D019076:Transgenes; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000939:Epitopes; D016056:Immunodominant Epitopes; D018396:Mucin-1